Publications

TitleAbstractYear
Filter
PMID
Filter
treatment of autochthonous rat brain tumors with fractionated radiotherapy. the effects of graded radiation doses and of combined therapy with bcnu or steroids.the avian sarcoma virus-induced glioma model in rats was used to evaluate radiation dose response (survival curves), giving fractionated treatments to the whole head. groups of 14 to 20 rats received total doses of 2300, 4600, or 5750 rads over 2, 4, or 5 weeks, respectively. median group survival times were compared to controls and to each other. all doses of radiation significantly prolonged survival with reference to control. the 4600- and 5750-rad doses were significantly more effective than ...19807411210
expression of the v-crk oncogene product in pc12 cells results in rapid differentiation by both nerve growth factor- and epidermal growth factor-dependent pathways.the transforming gene of the avian sarcoma virus ct10 encodes a fusion protein (p47gag-crk or v-crk) containing viral gag sequences fused to cellular sequences consisting primarily of src homology regions 2 and 3 (sh2 and sh3 sequences). here we report a novel function of v-crk in the mammalian pheochromocytoma cell line, pc12, whereby stable expression of v-crk induces accelerated differentiation, as assessed by induction of neurites following nerve growth factor (ngf) or basic fibroblast growt ...19947509449
high-resolution structure of the catalytic domain of avian sarcoma virus integrase.retroviral integrase (in) functions to insert retroviral dna into the host cell chromosome in a highly coordinated manner. in catalyzes two biochemically separable reactions: processing of the viral dna ends and joining of these ends to the host dna. previous studies suggested that these two reactions are chemically similar and are carried out by a single active site that is characterized by a highly conserved constellation of carboxylate residues, the d,d(35)e motif. we report here the crystal ...19957563093
identification and characterization of a high-affinity interaction between v-crk and tyrosine-phosphorylated paxillin in ct10-transformed fibroblasts.the genome of avian sarcoma virus ct10 encodes a fusion protein in which viral gag sequences are fused to cellular crk sequences containing primarily src homology 2 (sh2) and src homology 3 (sh3) domains. transformation of chicken embryo fibroblasts (cef) with the gag-crk fusion protein results in the elevation of tyrosine phosphorylation on specific cellular proteins with molecular weights of 130,000, 110,000, and 70,000 (p130, p110, and p70, respectively), an event which has been correlated wi ...19937687742
avian cellular homolog of the qin oncogene.we have isolated chicken cdna clones of the c-qin gene, the cellular counterpart of the v-qin (chinese for "avian") oncogene of avian sarcoma virus 31. there are several differences between the cellular and the viral qin sequences: (i) two nonconservative amino acid substitutions in the qin coding region; (ii) a truncation in the carboxyl terminus of the viral protein due to a premature stop codon; (iii) a partial gag sequence fused to the amino terminus of viral qin; and (iv) eight cell-coded a ...19957831308
new case of c-src gene transduction: the generation of virus pr2257.pr2257 is a new replication-defective avian sarcoma virus which harbours in addition to the spliced version of the c-src gene also about 950 bp of no-coding cellular sequences located downstream from the c-src stop codon (geryk et al., 1989). comparison of the 950 bp region transduced by pr2257 with the chicken c-src cdna (dorai et al., 1991) and genomic sequences of the c-src 3' non-coding region from chicken and quail has shown that there are no additional introns. the c-src 3' non-coding regi ...19947895852
abl protein-tyrosine kinase selects the crk adapter as a substrate using sh3-binding sites.to understand the normal and oncogenic functions of the protein-tyrosine kinase abl, the yeast two-hybrid system has been used for identifying proteins that interact with it. one interacting protein is crk-i, an sh3/sh2-containing adapter protein that was originally identified as the oncogenic element in the avian sarcoma virus ct10. direct interaction between the crk-i sh3 and abl at novel, approximately 10 amino acid sites just carboxy-terminal to the abl kinase domain occurs in vitro and in m ...19947926767
the 3' region of c-src gene mrna is entirely included in exon 12 and does not encode another protein.we previously reported the isolation of pr2257, a novel replication defective avian sarcoma virus which transduced the entire c-src coding region together with about 900 bp of c-src 3' non coding sequences. this virus originated from a chicken sarcoma induced by inoculation of a transformation-defective rous sarcoma virus carrying only replicative genes. the 5' end of pr2257 was formed by a splice junction between viral leader sequences and the first exon of c-src. to understand the mechanism of ...19948049278
crkl is the major tyrosine-phosphorylated protein in neutrophils from patients with chronic myelogenous leukemia.the philadelphia chromosome (ph1), detected in virtually all cases of chronic myelogenous leukemia (cml), is formed by a reciprocal translocation between chromosome 9 and 22 that fuses bcr-encoded sequences upstream of exon 2 of c-abl. this oncogene produces a fusion protein, p210bcr-abl, in which the abl tyrosine kinase activity is elevated. using anti-phosphotyrosine immunoblotting, we have compared the pattern of phosphotyrosine-containing proteins from freshly prepared neutrophils of patient ...19948083188
the retroviral oncogene qin belongs to the transcription factor family that includes the homeotic gene fork head.avian sarcoma virus 31 contains an oncogene that we have named qin. qin codes for a nuclear protein, qin, that is a member of the hnf-3/fork head family of transcriptional regulators. within this family qin is particularly closely related to rat brain factor 1 (bf-1), a telencephalon-specific gene presumed to play an important role in the development of the mammalian brain.19938099441
impact of stereotactic interstitial radiation on brain capillary physiology.rcbf, capillary permeability and vascular volume have been measured during the time course of interstitial stereotactic radiosurgery in normal and tumour-bearing dog brain. for rcbf measurement the stable xenon-ct-technique with a modified kety-schmidt equation has been used, and for measurement of blood-to-brain transport of meglumine iothalamate the two-compartment ct-method as developed by groothuis, which also reflects vascular volume. anaplastic gliomas had been induced by intracerebral inj ...19938109311
frameshift mutations in the v-src gene of avian sarcoma virus act in cis to specifically reduce v-src mrna levels.a portion of the avian sarcoma virus (asv) primary rna transcripts is alternatively spliced in chicken embryo fibroblast cells to two different messages, the src and env mrnas. frameshift mutations of the viral genome causing premature translation termination within the src gene result in a decreased steady-state level of the src mrna. in marked contrast, frameshift mutations at various positions of the env gene do not decrease the level of the env mrna. we show that the src gene product is not ...19948114716
a base-paired structure in the avian sarcoma virus 5' leader is required for efficient encapsidation of rna.selective encapsidation of avian sarcoma-leukosis virus genomic rna within virions requires recognition of a cis-acting signal (termed psi) located in the 5' leader of the rna between the primer binding site and the splice donor site. computer analyses indicate the potential for numerous secondary structure interactions within this region, including alternative conformations with similar free energy levels. we have constructed mutations designed to disrupt and restore potential secondary structu ...19948207823
generation of cytotoxic immune responses during the progression of a rat glioma.cytotoxic t lymphocytes specific for tumor-associated antigens are produced by exposing animals to tumor cells and stimulating lymphocytes from animals immunized in vitro with tumor cells and small amounts of interleukin-2 (il-2). this study was designed to determine whether a fast-growing immunogenic avian sarcoma virus-induced glioma produces primed cytotoxic t lymphocyte precursors during its progression. lymphocytes from intracerebral glioma-bearing rats generally failed to proliferate in vi ...19948271027
avian sarcoma virus rna synthesis, rna splicing and virus production in human foreskin fibroblasts: effect of co-infection with human cytomegalovirus.the level of rna transcripts in human foreskin fibroblast (hff) cells initiated from the avian sarcoma virus (asv) long terminal repeat (ltr) promoter was stimulated more than 10-fold when the cells were also infected with human cytomegalovirus (hcmv). hcmv was able to stimulate transcription from the asv ltr promoter even when all the ltr sequence upstream of the tata box was deleted, suggesting that only the basal ltr promoter is required for the effect. there were no significant changes in th ...19938277268
ala-->gly mutation in the putative catalytic loop confers temperature sensitivity on ros, insulin receptor, and insulin-like growth factor i receptor protein-tyrosine kinases.temperature-sensitive mutations in the avian sarcoma virus ur2 oncogene ros, encoding a receptor protein-tyrosine kinase (ptk), were identified. the ala385-->gly change mapping within the highly conserved rdlaarn motif in the ros kinase domain was responsible for the temperature-sensitive phenotype. based on the sequence homology of all known protein kinases and the crystalline structure of the camp-dependent protein kinase, this conserved region probably represents the ptk catalytic loop. the s ...19948278385
c-jun is essential for normal mouse development and hepatogenesis.the proto-oncogene c-jun is the cellular homologue of v-jun, the transforming oncogene of the avian sarcoma virus 17 (ref. 1). c-jun encodes one major component of the ap-1 transcription factor complex and is expressed in many organs during mouse development and in the adult. because of its rapid induction in cells following growth stimulation and the presence of ap-1 binding sites in the promoter regions of many genes, the c-jun protein is thought to have important functions in cell proliferati ...19938371760
modulating effects of the extracellular sequence of the human insulinlike growth factor i receptor on its transforming and tumorigenic potential.we reported previously that an n-terminally truncated insulinlike growth factor i receptor (igfr) fused to avian sarcoma virus ur2 gag p19 had a greater transforming potential than did the native igfr, but it failed to cause tumors in vivo. to investigate whether the 36 amino acids (aa) of the igfr extracellular (ec) sequence in the gag-igfr fusion protein encoded by the retrovirus uigfr have a modulatory effect on the biological and biochemical properties of the protein, four mutants, nm1, nm2, ...19938380100
molecular and biochemical bases for activation of the transforming potential of the proto-oncogene c-ros.the transforming gene of avian sarcoma virus ur2, v-ros, encodes a receptor-like protein tyrosine kinase and differs from its proto-oncogene, c-ros, in its 5' truncation and fusion to viral gag, a three-amino-acid (aa) insertion in the transmembrane (tm) domain, and changes in the carboxyl region. to explore the basis for activation of the c-ros transforming potential, various c-ros retroviral vectors containing those changes were constructed and studied for their biological and biochemical prop ...19938411348
morphological and biochemical analyses of contractile proteins (actin, myosin, caldesmon and tropomyosin) in normal and transformed cells.the expression and intracellular distribution of four contractile proteins (actin, myosin, caldesmon and tropomyosin) in normal fibroblasts and their transformed counterparts by rous or avian sarcoma virus were compared. by analyzing the isoformal expression of actin, caldesmon and tropomyosin using two-dimensional gel electrophoresis, only tropomyosin showed significant alteration in its isoformal expression accompanied by transformation. morphological study revealed that in normal cells, myosi ...19938505382
the effects of dexamethasone on transcapillary transport in experimental brain tumors: ii. canine brain tumors.we studied the effect of dexamethasone on transcapillary transport in ten avian sarcoma virus (asv)-induced canine brain tumors, before and one week after administration of dexamethasone, 2.5 mg/kg/day. a computed tomographic (ct) method was used to measure regional values of k1 (blood-to-tissue transfer constant), k2 (tissue-to-blood efflux constant), and vp (tissue plasma vascular space) of meglumine iothalamate (conray-60); the values were reconstructed for each 0.8 x 0.8 x 5 mm volume elemen ...19958523087
possible v-crk-induced transformation through activation of src kinases.p47gag-crk (v-crk) encoded by avian sarcoma virus ct10, causes an elevation of tyrosine phosphorylation of several cellular proteins. the lack of a protein-tyrosine kinase domain in v-crk suggests its co-operation with cellular protein-tyrosine kinase activity. we have shown that suppression of a certain fraction of c-src activity by csk may require the binding of csk to tyrosine-phosphorylated paxillin. in this study, we detected co-immunoprecipitation of tyrosine-phosphorylated paxillin with v ...19958537387
a recombinant fowlpox virus expressing the envelope antigen of subgroup a avian leukosis/sarcoma virus.a recombinant fowlpox virus (fpv) was constructed by inserting cloned sequences from schmidt-ruppin subgroup a avian sarcoma virus coding for the viral envelope (env) antigen into a nonessential region of fpv dna downstream from a synthetic promoter. sera from chickens hyperimmunized with the recombinant fpv neutralized the infectivity of the homologous subgroup a virus (rcasbp/ap) but only weakly neutralized the infectivity of rous sarcoma virus, another subgroup a avian leukosis virus. similar ...19958561735
targeting of retroviral integrase by fusion to a heterologous dna binding domain: in vitro activities and incorporation of a fusion protein into viral particles.retroviral dna integration is catalyzed by a viral protein, the integrase (in). in recognizes sequences at the viral dna ends, specifically nicks these ends (the processing reaction), and inserts them into host dna (the joining reaction). the mechanism by which host dna integration sites are selected is unknown, although it is clear that many regions are accessible to the retroviral integration machinery. to investigate integration site selection, and to possibly influence this process, we have ...19968599202
concerted integration of linear retroviral dna by the avian sarcoma virus integrase in vitro: dependence on both long terminal repeat termini.we have reconstituted integration reactions in vitro with specially designed donor dnas, a supercoiled plasmid acceptor, purified bacterium-derived rous sarcoma virus integrase (in), and a host cell dna-bending protein, hmg1. the duplex donor dnas are approximately 300 deoxynucleotides in length and contain only 15 bp of the rsv u3 and u5 termini at the respective ends. the donor has blunt u3 and u5 termini which end with the sequence 5'catt. joining of the donor dna to the acceptor dna is detec ...19968648691
influence of the transduced 3'utr of the c-src oncogene on tumour growth induced by the v-src gene of avian sarcoma virus pr2257.avian sarcoma virus pr2257 contains 952 bp transduced from the left part of the 3'utr of the chicken c-src oncogene. deletion mutants were constructed to determine the effect of the 3'utr on tumorigenicity in vivo and in vitro. in the presence of the 3'utr, tumours were 3.4 times larger in vivo, and tumorigenicity was increased 2.5-fold in vitro. several regulatory submotifs were also found within the 3'utr. parts of the 3'utr were cloned into the ltr cat plasmid and analysed for cat expression. ...19968683206
retroviral integrases and their cousins.the recently determined structures of the catalytic domains of hiv integrase, avian sarcoma virus integrase and the mu transposase are strikingly similar to each other and also exhibit significant similarity to several nucleases. all these enzymes of cut polynucleotides, leaving 3'oh and 5'po4 groups. the integrase and transposase also possess a strand-transfer activity that splices dna. the structural similarities among members of this superfamily of polynucleotidyl transferases suggest that th ...19968696976
domains of the qin protein required for oncogenic transformation.the qin oncogene is a cell-derived insert in the genome of avian sarcoma virus 31 (asv 31) and functions as the oncogenic determinant of that virus. overexpression of the viral and cellular versions of the qin protein (v-qin and c-qin) induces oncogenic transformation of chicken embryo fibroblasts (cef); v-qin also rapidly induces fibrosarcomas in chickens. qin proteins can bind to specific dna sequences and act as transcriptional repressors. in this study, mutants of qin were constructed in ord ...19968710385
structural and functional characterization of a novel tumor-derived rat galectin-1 having transforming growth factor (tgf) activity: the relationship between intramolecular disulfide bridges and tgf activity.previously we demonstrated that overexpression of a beta-galactoside binding protein, galectin-1, caused the transformation of balb3t3 fibroblast cells [yamaoka, k., ohno, s., kawasaki, h., and suzuki, k. (1991) biochem. biophys. res. commun. 179, 272-279]. we have now studied the structure-function relationship between the sugar-binding activity and the mitogenic activity of galectin-1 purified from an avian sarcoma virus-transformed rat nrk cell line, 77n1. the purified galectin-1 (t-galectin- ...19968797087
the catalytic domain of avian sarcoma virus integrase: conformation of the active-site residues in the presence of divalent cations.members of the structurally-related superfamily of enzymes that includes rnase h, ruvc resolvase, mua transposase, and retroviral integrase require divalent cations for enzymatic activity. so far, cation positions are reported in the x-ray crystal structures of only two of these proteins, e. coli and human immunodeficiency virus 1 (hiv-1) rnase h. details of the placement of metal ions in the active site of retroviral integrases are necessary for the understanding of the catalytic mechanism of t ...19968805516
a role for ras in v-crk transformation.the v-crk oncogene, identified as the transforming gene of the ct10 avian sarcoma virus, encodes an adaptor protein capable of transforming chicken embryo fibroblasts (cefs). because the src homology 3 domain of v-crk is capable of binding the ras family guanine nucleotide exchange factors sos and c3g, the contribution of cellular ras to signaling by v-crk was evaluated. nih-3t3 cell lines stably expressing the v-crk oncogene exhibited a transformed phenotype similar to that of ct10-infected cef ...19968930393
the catalytic domain of human immunodeficiency virus integrase: ordered active site in the f185h mutant.we solved the structure and traced the complete active site of the catalytic domain of the human immunodeficiency virus type 1 integrase (hiv-1 in) with the f185h mutation. the only previously available crystal structure, the f185k mutant of this domain, lacks one of the catalytically important residues, e152, located in a stretch of 12 disordered residues [dyda et al. (1994) science 266, 1981-1986]. it is clear, however, that the active site of hiv-1 in observed in either structure cannot corre ...19968977101
subcellular localization of avian sarcoma virus and human immunodeficiency virus type 1 integrases.the composition and subcellular trafficking of subviral preintegration complexes are reported to vary among the different retroviruses. the process by which the avian sarcoma virus (asv) preintegration complex gains access to target chromatin remains unknown. here we report that asv integrase (in) expressed as a fusion to beta-galactosidase accumulates in the nuclei of transfected cos-1 cells. in contrast, human immunodeficiency type 1 (hiv-1) in-beta-galactosidase fusions expressed similarly ar ...19978985428
suppression in transformed avian fibroblasts of a gene (co6) encoding a membrane protein related to mammalian potassium channel regulatory subunits.gene expression patterns in normal and v-myc-transformed quail embryo fibroblasts were compared by mrna differential display. displaying approximately 2500 mrna species by reverse transcription/pcr, reamplification of 73 differential cdna fragments and rescreening by northern analysis led to the isolation of a clone, termed co6, that hybridized to an mrna species present only in the normal but not in the transformed fibroblasts. further analyses revealed that the 0.95-kb co6 mrna was present in ...19979070660
decreased susceptibility to calpains of v-fosfbr but not of v-fosfbj or v-junasv17 retroviral proteins compared with their cellular counterparts.the c-fos and c-jun transcription factors are rapidly turned over in vivo. one of the multiple pathways responsible for their breakdown is probably initiated by calpains, which are cytoplasmic calcium-dependent cysteine proteases. the c-fos gene has been transduced by two murine oncogenic retroviruses called finkel-biskis-jenkins murine sarcoma virus (fbj-msv) and finkel-biskis-reilly murine sarcoma virus (fbr-msv); c-jun has been transduced by the chicken avian sarcoma virus 17 (asv17) retrovir ...19979169601
transformation of chicken cells by the gene encoding the catalytic subunit of pi 3-kinase.the avian sarcoma virus 16 (asv 16) is a retrovirus that induces hemangiosarcomas in chickens. analysis of the asv 16 genome revealed that it encodes an oncogene that is derived from the cellular gene for the catalytic subunit of phosphoinositide 3-kinase (pi 3-kinase). the gene is referred to as v-p3k, and like its cellular counterpart c-p3k, it is a potent transforming gene in cultured chicken embryo fibroblasts (cefs). the products of the viral and cellular p3k genes have pi 3-kinase activity ...19979188528
expression, purification, and initial characterization of human yes protein tyrosine kinase from a bacterial expression system.protein tyrosine kinase yes is a cellular homolog of v-yes, the oncogenic protein product of avian sarcoma virus y73. yes is a member of the src family and its activation has been associated with several types of human cancer. human yes has not been previously characterized enzymatically. to carry out biochemical characterizations of this enzyme, we expressed it as a fusion protein with glutathione s-transferase in escherichia coli, to allow purification in a single step. the affinity-purified g ...19979281320
cleavage of the x-pro peptide bond by pepsin is specific for the trans isomer.fluorine nuclear magnetic resonance studies of the cleavage of peptides containing a 4-fluorophenylalanine (fphe)-pro bond have been performed in order to determine the conformational specificity of fphe-pro bond cleavage by pepsin. the peptides selected were substrates of hiv protease or of avian sarcoma virus protease, both of which have been reported to be cleaved specifically at x-pro by pepsin as well as by the corresponding viral protease enzyme. by working at 0 degrees c, it was possible ...19979341212
molecular mechanisms in retrovirus dna integration.the integrase protein of retroviruses catalyzes the insertion of the viral dna into the genomes of the cells that they infect. integrase is necessary and sufficient for this recombination reaction in vitro; however, the enzyme's activity appears to be modulated in vivo by viral and cellular components included in the nucleoprotein pre-integration complex. in addition to integrase, cis-acting sequences at the ends of the viral dna are important for integration. solution of the structures of the i ...19979477115
rat brain tumor models in experimental neuro-oncology: the 9l, c6, t9, f98, rg2 (d74), rt-2 and cns-1 gliomas.rat brain tumor models have been widely used in experimental neuro-oncology for almost three decades. the present review, which will be selective rather than comprehensive, will focus entirely on seven rat brain tumor models and their utility in evaluating the efficacy of various therapeutic modalities. although no currently available animal brain tumor model exactly simulates human high grade brain tumors, the rat models that are currently available have provided a wealth of information on in v ...19989525831
structure of the catalytic domain of avian sarcoma virus integrase with a bound hiv-1 integrase-targeted inhibitor.the x-ray structures of an inhibitor complex of the catalytic core domain of avian sarcoma virus integrase (asv in) were solved at 1.9- to 2.0-a resolution at two ph values, with and without mn2+ cations. this inhibitor (y-3), originally identified in a screen for inhibitors of the catalytic activity of hiv type 1 integrase (hiv-1 in), was found in the present study to be active against asv in as well as hiv-1 in. the y-3 molecule is located in close proximity to the enzyme active site, interact ...19989560188
role of the constitutive splicing factors u2af65 and sap49 in suboptimal rna splicing of novel retroviral mutants.retroviruses display a unique form of alternative splicing in which both spliced and unspliced rnas accumulate in the cytoplasm. simple retroviruses, such as avian sarcoma virus, do not encode regulatory proteins that affect splicing; this process is controlled solely through interactions between the viral rna and the host cell splicing machinery. previously, we described the selection and characterization of novel avian sarcoma virus mutants. these viruses were separated into two classes based ...19989614130
nucleotide sequence of the murine leukaemia virus amphotropic strain 4070a integrase (in) coding region and comparative structural analysis of the inferred polypeptide.the complete nucleotide sequence of the integrase (in) protein coding region of the murine leukaemia virus (mlv) amphotropic strain 4070a is presented. the sequence comprises 1,224 nucleotides, encoding a 408-residue polypeptide of m(r) 46,312. alignment of the inferred 4070a in amino acid sequence with the in proteins of other mlv showed that substitutions are confined largely to segments within the n- and c-terminal domains. in the n-terminal domain the majority of substitutions occur as conti ...19979672635
a preferred target dna structure for retroviral integrase in vitro.the retroviral integrase protein catalyzes the insertion of linear viral dna ends into the host cell dna. although integration in vivo is not site-specific, the detection of local and regional preferences within cellular dna suggests that the integration reaction can be influenced by specific features of host dna or chromatin. here we describe highly preferred in vitro integration sites for avian sarcoma virus and human immunodeficiency virus-1 integrases within the stems of plasmid dna crucifor ...19989727042
the core domain of retrotransposon integrase in hordeum: predicted structure and evolution.propagation of long terminal repeat (ltr)-bearing retrotransposons and retroviruses requires integrase (in, ec 2.7.7.-), encoded by the retroelements themselves, which mediates the insertion of cdna copies back into the genome. an active retrotransposon family, bare-1, comprises approximately 7% of the barley (hordeum vulgare subsp. vulgare) genome. we have generated models for the secondary and tertiary structure of bare-1 in and demonstrate their similarity to structures for human immunodefici ...19989729878
activation of the insulin-like growth factor type 1 receptor by deletion of amino acids 870-905.we have created a deletion mutant of the insulin-like growth factor type 1 receptor (igf-1 r) which lacks the 36 amino acids (aa) immediately n-terminal to the transmembrane domain (delta870-905 igf-1 r). this region has been reported to have a negative effect on the transforming potential of an avian sarcoma virus gag-igf-1 r fusion protein. we have sought to determine whether this region plays a similar role in the intact igf-1 r. analysis of the tyrosine kinase activity of the delta870-905 ig ...19989743592
characterization of the nuclear localization signal in the avian sarcoma virus integrase.a sequence of 21 amino acids (aa) in the c-terminal region of the 286-aa avian sarcoma virus (asv) integrase (in) protein has been shown previously to mediate nuclear localization of both in and beta-galactosidase (betagal) protein fused to it. this karyophilic sequence includes a high proportion of prolines and residues with basic side chains. in this report, site-directed mutagenesis was used to introduce single aa substitutions of several of these residues. indirect immunofluorescence showed ...19989858717
hmg protein family members stimulate human immunodeficiency virus type 1 and avian sarcoma virus concerted dna integration in vitro.we have reconstituted concerted human immunodeficiency virus type 1 (hiv-1) integration in vitro with specially designed mini-donor hiv-1 dna, a supercoiled plasmid acceptor, purified bacterium-derived hiv-1 integrase (in), and host hmg protein family members. this system is comparable to one previously described for avian sarcoma virus (asv) (a. aiyar et al., j. virol. 70:3571-3580, 1996) that was stimulated by the presence of hmg-1. sequence analyses of individual hiv-1 integrants showed loss ...199910074149
the three-dimensional structure of a tn5 transposase-related protein determined to 2.9-a resolution.transposon tn5 employs a unique means of self-regulation by expressing a truncated version of the transposase enzyme that acts as an inhibitor. the inhibitor protein differs from the full-length transposase only by the absence of the first 55 n-terminal amino acid residues. it contains the catalytic active site of transposase and a c-terminal domain involved in protein-protein interactions. the three-dimensional structure of tn5 inhibitor determined to 2.9-a resolution is reported here. a portio ...199910207011
x-ray structure of simian immunodeficiency virus integrase containing the core and c-terminal domain (residues 50-293)--an initial glance of the viral dna binding platform.the crystal structure of simian immunodeficiency virus (siv) integrase that contains in a single polypeptide the core and the c-terminal deoxyoligonucleotide binding domain has been determined at 3 a resolution with an r-value of 0.203 in the space group p2(1)2(1)2(1). four integrase core domains and one c-terminal domain are found to be well defined in the asymmetric unit. the segment extending from residues 114 to 121 assumes the same position as seen in the integrase core domain of avian sarc ...200010669606
identification of hiv-1 integrase inhibitors via three-dimensional database searching using asv and hiv-1 integrases as targets.integration of viral dna into the host cell genome is a critical step in the life cycle of hiv. this essential reaction is catalyzed by integrase (in) through two steps, 3'-processing and dna strand transfer. integrase is an attractive target for drug design because there is no known cellular analogue and integration is essential for successful replication of hiv. a computational three-dimensional (3-d) database search was used to identify novel hiv-1 integrase inhibitors. starting from the prev ...200011058033
base-pair substitutions in avian sarcoma virus u5 and u3 long terminal repeat sequences alter the process of dna integration in vitro.we have described a reconstituted avian sarcoma virus (asv) concerted dna integration system with specially designed mini-donor dna containing a supf transcription unit, a supercoiled plasmid acceptor, purified bacterially expressed asv integrase (in), and human high-mobility-group protein i(y). integration in this system is dependent upon the mini-donor dna having in recognition sequences at both ends and upon both ends of the same donor integrating into the acceptor dna. the integrated dna pro ...200111152486
wortmannin potentiates integrase-mediated killing of lymphocytes and reduces the efficiency of stable transduction by retroviruses.retroviral infection induces integrase-dependent apoptosis in dna-pk-deficient murine scid lymphocytes. furthermore, the efficiency of stable transduction of reporter genes is reduced in adherent cell lines that are deficient in cellular dna-repair proteins known to mediate nonhomologous end joining (nhej), such as dna-pk and xrcc4 (r. daniel, r. a. katz, and a. m. skalka, science 284:644-647, 1999). here we report that wortmannin, an irreversible inhibitor of phosphatidylinositol 3-kinase (pi-3 ...200111158303
role of dna end distortion in catalysis by avian sarcoma virus integrase.retroviral integrase (in) recognizes linear viral dna ends and introduces nicks adjacent to a highly conserved ca dinucleotide usually located two base pairs from the 3'-ends of viral dna (the "processing" reaction). in a second step, the same in active site catalyzes the insertion of these ends into host dna (the "joining" reaction). both dna sequence and dna structure contribute to specific recognition of viral dna ends by in. here we used potassium permanganate modification to show that the a ...200111441016
growth arrest and dna damage-inducible protein gadd34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1.the growth arrest and dna damage-inducible protein, gadd34, was identified by its interaction with human inhibitor 1 (i-1), a protein kinase a (pka)-activated inhibitor of type 1 protein serine/threonine phosphatase (pp1), in a yeast two-hybrid screen of a human brain cdna library. recombinant gadd34 (amino acids 233 to 674) bound both pka-phosphorylated and unphosphorylated i-1(1-171). serial truncations mapped the c terminus of i-1 (amino acids 142 to 171) as essential for gadd34 binding. in c ...200111564868
jac, a direct target of oncogenic transcription factor jun, is involved in cell transformation and tumorigenesis.using subtractive hybridization techniques, we have isolated a gene termed jac that is strongly and specifically activated in avian fibroblasts transformed by the v-jun oncogene of avian sarcoma virus 17 (asv17), but not in cells transformed by other oncogenic agents. furthermore, jac is highly expressed in cell lines derived from jun-induced avian fibrosarcomas. kinetic analysis using a doxycycline-controlled conditional cell transformation system showed that expression of the 0.8-kb jac mrna i ...200111698665
changes in the mechanism of dna integration in vitro induced by base substitutions in the hiv-1 u5 and u3 terminal sequences.we have reconstituted concerted human immunodeficiency virus type 1 (hiv-1) integration with specially designed mini-donor dna, a supercoiled plasmid acceptor, purified bacterial-derived hiv-1 integrase (in), and host hmg-i(y) protein (hindmarsh, p., ridky, t., reeves, r., andrake, m., skalka, a. m., and leis, j. (1999) j. virol. 73, 2994-3003). integration in this system is dependent upon the mini donor dna having in recognition sequences at both ends and the reaction products have all of the f ...200211788585
presteady-state analysis of avian sarcoma virus integrase. i. a splicing activity and structure-function implications for cognate site recognition.integrase catalyzes insertion of a retroviral genome into the host chromosome. after reverse transcription, integrase binds specifically to the ends of the duplex retroviral dna, endonucleolytically cleaves two nucleotides from each 3'-end (the processing activity), and inserts these ends into the host dna (the joining activity) in a concerted manner. in first-turnover experiments with synapsed dna substrates, we observed a novel splicing activity that resembles an integrase joining reaction but ...200211821409
a cellular protein phosphorylated by the avian sarcoma virus transforming gene product is associated with ribonucleoprotein particles.in chick embryo fibroblasts transformed by rous sarcoma virus (rsv) the tyrosine phosphorylation of a cellular protein of 34,000 daltons mol. wt. (34 kd) is greatly enhanced; this was shown to be catalyzed by the phosphotransferase activity of rsv transforming protein pp60src. we report here that in cytoplasmic extracts of both normal and transformed cells, in the presence of magnesium ions, the majority of the 34-kd protein is associated with large structures and that a fraction of 34 kd appear ...198311894943
molecular and immunohistochemical analysis of signaling adaptor protein crk in human cancers.crk is a signaling adaptor protein which is mostly composed of sh2 and sh3 domains, and has been shown to play a pivotal role in cell proliferation, differentiation, and migration. because crk was originally isolated as an avian sarcoma virus ct10 encoding oncoprotein v-crk, we examined a potential role for c-crk in the carcinogenesis of human cancers. first, to analyze gene mutations of c-crk, we isolated a human bacterial artificial chromosome clone containing crk genome and exon/intron struct ...200211911970
transduction of interphase cells by avian sarcoma virus.it has been generally believed that oncoretroviruses are dependent on mitosis for efficient nuclear entry of viral dna. we previously identified a nuclear localization signal in the integrase protein of an oncoretrovirus, avian sarcoma virus (asv), suggesting an active import mechanism for the integrase-dna complex (g. kukolj, r. a. katz, and a. m. skalka, gene 223:157-163, 1998). here, we have evaluated the requirement for mitosis in nuclear import and integration of asv dna. using a modified a ...200211991971
mutations of the rnase h c helix of the moloney murine leukemia virus reverse transcriptase reveal defects in polypurine tract recognition.both the rnase h domain of moloney murine leukemia virus (mo-mlv) reverse transcriptase (rt) and escherichia coli rnase h possess a positively charged alpha-helix (c helix) and a loop that are not present in the rnase h domains of human immunodeficiency virus (hiv) rt or avian sarcoma virus rt. although a mutant mo-mlv rt lacking the c helix (deltac rt) retains dna polymerase activity on homopolymeric substrates and partial rnase h activity, reverse transcription of the viral rna genome in vivo ...200212134040
v-crk activates the phosphoinositide 3-kinase/akt pathway by utilizing focal adhesion kinase and h-ras.v-crk, an oncogene product of avian sarcoma virus ct10, efficiently transforms chicken embryo fibroblasts (cef). we have recently reported that constitutive activation of the phosphoinositide 3-kinase (pi3k)/akt pathway plays a critical role in the v-crk-induced transformation of cef. in the present study we investigated the molecular mechanism by which v-crk activates the pi3k/akt pathway. first, we found that v-crk promotes the association of the p85 regulatory subunit of pi3k with focal adhes ...200212242282
functional oligomeric state of avian sarcoma virus integrase.retroviral integrase, one of only three enzymes encoded by the virus, catalyzes the essential step of inserting a dna copy of the viral genome into the host during infection. using the avian sarcoma virus integrase, we demonstrate that the enzyme functions as a tetramer. in presteady-state active site titrations, four integrase protomers were required for a single catalytic turnover. volumetric determination of integrase-dna complexes imaged by atomic force microscopy during the initial turnover ...200312446721
matrix-independent activation of phosphatidylinositol 3-kinase, stat3, and cyclin a-associated cdk2 is essential for anchorage-independent growth of v-ros-transformed chicken embryo fibroblasts.the question remains open whether the signaling pathways shown to be important for growth and transformation in adherent cultures proceed similarly and play similar roles for cells grown under anchorage-independent conditions. chicken embryo fibroblasts (cef) infected with the avian sarcoma virus ur2, encoding the oncogenic receptor protein-tyrosine kinase (rptk) v-ros, or with two of its transformation-impaired mutants were grown in nonadherent conditions in methylcellulose (mc)-containing medi ...200312646574
evidence that the retroviral dna integration process triggers an atr-dependent dna damage response.caffeine is an efficient inhibitor of cellular dna repair, likely through its effects on atm (ataxia telangiectasia mutated) and atr (atm and rad3-related) kinases. here, we show that caffeine treatment causes a dose-dependent reduction in the total amount of hiv-1 and avian sarcoma virus retroviral vector dna that is joined to host dna in the population of infected cells and also in the number of transduced cells. these changes were observed at caffeine concentrations that had little or no effe ...200312679521
characterization of a naphthalene derivative inhibitor of retroviral integrases.the retroviral integrase protein (in) is essential for virus replication and, therefore, an attractive target for the development of inhibitors to treat human immunodeficiency virus (hiv) infection. diverse classes of compounds that are active against this protein have been discovered using in vitro assays. here we describe the synthesis of a novel compound, 3,8-dibromo-7-amino-4-hydroxy-2-naphthalenesulfonic acid (2brnsa), which inhibits the in vitro activities of the full-length hiv-1 and avia ...200415018700
transduction of terminally differentiated neurons by avian sarcoma virus.recent studies have demonstrated that avian sarcoma virus (asv) can transduce cycle-arrested cells. here, we have assessed quantitatively the transduction efficiency of an asv vector in naturally arrested mouse hippocampal neurons. this efficiency was determined by comparing the number of transduced cells after infection of differentiated neurons versus dividing progenitor cells. the results indicate that asv is able to transduce these differentiated neurons efficiently and that this activity is ...200415078971
integrase-specific enhancement and suppression of retroviral dna integration by compacted chromatin structure in vitro.integration of viral dna into the host chromosome is an obligatory step in retroviral replication and is dependent on the activity of the viral enzyme integrase. to examine the influence of chromatin structure on retroviral dna integration in vitro, we used a model target comprising a 13-nucleosome extended array that includes binding sites for specific transcription factors and can be compacted into a higher-ordered structure. we found that the efficiency of in vitro integration catalyzed by hu ...200415140982
genome-wide analyses of avian sarcoma virus integration sites.the chromosomal features that influence retroviral integration site selection are not well understood. here, we report the mapping of 226 avian sarcoma virus (asv) integration sites in the human genome. the results show that the sites are distributed over all chromosomes, and no global bias for integration site selection was detected. however, rna polymerase ii transcription units (protein-encoding genes) appear to be favored targets of asv integration. the integration frequency within genes is ...200415479807
integrase of mason-pfizer monkey virus.the gene encoding an integrase of mason-pfizer monkey virus (m-pmv) is located at the 3'-end of the pol open reading frame. the m-pmv integrase has not been previously isolated and characterized. we have now cloned, expressed, isolated, and characterized m-pmv integrase and compared its activities and primary structure with those of hiv-1 and other retroviral integrases. m-pmv integrase prefers untranslated 3'-region-derived long-terminal repeat sequences in both the 3'-processing and the strand ...200515634344
[characteristic of the two-step rna dimerization in avian sarcoma and leukosis viruses].dimerization of two copies of genomic rna is a necessary step of retroviral replication. in the case of human immunodeficiency virus type 1 (hiv-1) the process is explored in many details. it is proved that conserved stem-loop structure is an essential element in rna dimerization. similar model of two-step dimerization mechanism can be considered for avian sarcoma and leukosis virus group (aslv) in spite of the absence of homology between dimer initiation site (dis) of aslv and that of hiv-1. in ...200515773559
the cellular protein daxx interacts with avian sarcoma virus integrase and viral dna to repress viral transcription.the cellular protein daxx was identified as an interactor with avian sarcoma virus (asv) integrase (in) in a yeast two-hybrid screen. after infection, daxx-in interactions were detected by coimmunoprecipitation. an association between daxx and viral dna, likely mediated by in, was also detected by chromatin immunoprecipitation. daxx was not required for early events in asv replication, including integration, as daxx-null cells were transduced as efficiently as daxx-expressing cells. however, vir ...200515795247
neuregulin-regulated gene expression in mammary carcinoma cells.recent studies have suggested that autocrine production of neuregulin (nrg), a growth factor that activates members of the epidermal growth factor receptor/erbb family of proto-oncogenes, is sufficient for breast tumor initiation and progression. to elucidate the molecular mechanisms regulating these events, we undertook a global analysis of genes regulated by nrg in luminal mammary epithelial cell lines. gene expression profiling of estrogen receptor-positive t47d cells exposed to nrg-1 reveale ...200515963498
identification of amino acids in hiv-1 and avian sarcoma virus integrase subsites required for specific recognition of the long terminal repeat ends.a tetramer model for hiv-1 integrase (in) with dna representing 20 bp of the u3 and u5 long terminal repeats (ltr) termini was assembled using structural and biochemical data and molecular dynamics simulations. it predicted amino acid residues on the enzyme surface that can interact with the ltr termini. a separate structural alignment of hiv-1, simian sarcoma virus (siv), and avian sarcoma virus (asv) ins predicted which of these residues were unique. to determine whether these residues were re ...200616298997
acquisition of new dna sequences after infection of chicken cells with avian myeloblastosis virus.dna-rna hybridization studies between 70s rna from avian myeloblastosis virus (amv) and an excess of dna from (i) amv-induced leukemic chicken myeloblasts or (ii) a mixture of normal and of congenitally infected k-137 chicken embryos producing avian leukosis viruses revealed the presence of fast- and slow-hybridizing virus-specific dna sequences. however, the leukemic cells contained twice the level of amv-specific dna sequences observed in normal chicken embryonic cells. the fast-reacting seque ...197416789139
high-frequency epigenetic repression and silencing of retroviruses can be antagonized by histone deacetylase inhibitors and transcriptional activators, but uniform reactivation in cell clones is restricted by additional mechanisms.integrated retroviral dna is subject to epigenetic gene silencing, but the viral and host cell properties that influence initiation, maintenance, and reactivation are not fully understood. here we describe rapid and high-frequency epigenetic repression and silencing of integrated avian sarcoma virus (asv)-based vector dnas in human hela cells. initial studies utilized a vector carrying the strong human cytomegalovirus (hcmv) immediate-early (ie) promoter to drive expression of a green fluorescen ...200717202206
effect of targeting janus kinase 3 on the development of intestinal tumors in the adenomatous polyposis coli(min) mouse model of familial adenomatous polyposis.familial adenomatous polyposis (fap) is associated with germ-line mutations in the tumor suppressor gene, adenomatous polyposis coli (apc) located on chromosome 5q21. multiple intestinal neoplasia (min) in mice resembles fap in humans, resulting from a single point mutation in the murine homolog of the apc gene. the effects of the rationally-designed janus kinase 3 (jak3) inhibitor janex-1 (4-(4'-hydroxyphenyl) amino-6,7-dimethoxy-quinazoline, whi-p131, cas 202475-60-3) on the development of int ...200717688077
loop202-208 in avian sarcoma virus integrase mediates tetramer assembly and processing activity.integrase (in) catalyzes insertion of the retroviral genome into the host via two sequential reactions. the processing activity cleaves the 3'-dinucleotides from the two ends of the viral dna which are then inserted into the host dna. tetramers are required for the joining step. while dimers have been shown to catalyze processing, they do so inefficiently, and the oligomeric requirement for processing is unknown. we have replaced loop202-208 at the putative dimer-dimer interface of the avian sar ...200717845008
a single-amino-acid substitution in the tvbs1 receptor results in decreased susceptibility to infection by avian sarcoma and leukosis virus subgroups b and d and resistance to infection by subgroup e in vitro and in vivo.the avian sarcoma and leukosis virus (aslv) family of retroviruses contains five highly related envelope subgroups (a to e) thought to have evolved from a common viral ancestor in the chicken population. three genetic loci in chickens determine the susceptibility or resistance of cells to infection by the subgroup a to e aslvs. some inbred lines of chickens display phenotypes that are somewhere in between either efficiently susceptible or resistant to infection by specific subgroups of aslv. the ...200818094190
identification of cellular proteins that maintain retroviral epigenetic silencing: evidence for an antiviral response.integrated retroviral dna is subject to epigenetic gene silencing, resulting in loss of expression of viral genes as well as reporter or therapeutic genes transduced by retroviral vectors. possible mediators of such silencing include the histone deacetylase (hdac) family of cellular proteins. we previously isolated hela cell populations that harbored silent avian sarcoma virus-based green fluorescent protein (gfp) vectors that could be reactivated by treatment with hdac inhibitors. here, we deve ...200818094192
tsg101 can replace nedd4 function in asv gag release but not membrane targeting.the late (l) domain of the avian sarcoma virus (asv) gag protein binds nedd4 ubiquitin ligase e3 family members and is the determinant of efficient virus release in avian and mammalian cells. we previously demonstrated that nedd4 and tsg101 constitutively interact raising the possibility that nedd4 links asv gag to the escrt machinery. we now demonstrate that covalently linking tsg101 to asv gag lacking the nedd4 binding site (deltap2b-tsg101) ablates the requirement for nedd4, but the rescue of ...200818555885
toj3, a v-jun target with intrinsic oncogenic potential, is directly regulated by jun via a novel ap-1 binding motif.the toj3 gene was originally identified on the basis of its specific activation in avian fibroblasts transformed by the v-jun oncogene of avian sarcoma virus 17 (asv17). overexpression of toj3 induces cellular transformation of embryonic avian fibroblasts, revealing an intrinsic oncogenic potential. transforming activity has also been demonstrated for msp58, the human homolog of toj3, and oncogenic cell transformation by msp58 is specifically inhibited by the tumor suppressor pten. to investigat ...200818603277
avian sarcoma virus and human immunodeficiency virus, type 1 use different subsets of escrt proteins to facilitate the budding process.members of the nedd4 family of e3 ubiquitin ligases bind the l domain in avian sarcoma virus (asv) gag and facilitate viral particle release. translational fusion of asv gag with an l domain deletion (deltap2b) to proteins that comprise escrt-i, -ii, and -iii (the endocytic sorting complexes required for transport) rescued both gag ubiquitination and particle release from cells. the escrt-i factors vps37c or tsg101 were more effective in rescue of gag/deltap2b budding than the escrt-ii factor ea ...200818723511
defining the dna substrate binding sites on hiv-1 integrase.a tetramer model for human immunodeficiency virus type 1 (hiv-1) integrase (in) with dna representing long terminal repeat (ltr) termini was previously assembled to predict the in residues that interact with the ltr termini; these predictions were experimentally verified for nine amino acid residues [chen, a., weber, i. t., harrison, r. w. & leis, j. (2006). identification of amino acids in hiv-1 and avian sarcoma virus integrase subsites required for specific recognition of the long terminal re ...200919014951
functional and structural characterization of the integrase from the prototype foamy virus.establishment of the stable provirus is an essential step in retroviral replication, orchestrated by integrase (in), a virus-derived enzyme. until now, available structural information was limited to the ins of human immunodeficiency virus type 1 (hiv-1), avian sarcoma virus (asv) and their close orthologs from the lentivirus and alpharetrovirus genera. here, we characterized the in vitro activity of the prototype foamy virus (pfv) in from the spumavirus genus and determined the three-dimensiona ...200919036793
v-crk regulates membrane dynamics and rac activation.cell migration is an integrated process that involves cell adhesion, protrusion and contraction. we recently used cas (crk-associated substrate, 130cas)-deficient mouse embryo fibroblasts (mefs) to examined contribution made to v-crk to that process via its interaction with rac1. v-crk, the oncogene product of avian sarcoma virus ct10, directly affects membrane ruffle formation and is associated with rac1 activation, even in the absence of cas, a major substrate for crk. in cas-deficient mefs, c ...200819262107
rat brain tumor models in experimental neuro-oncology: the c6, 9l, t9, rg2, f98, bt4c, rt-2 and cns-1 gliomas.in this review we will describe eight commonly used rat brain tumor models and their application for the development of novel therapeutic and diagnostic modalities. the c6, 9l and t9 gliomas were induced by repeated injections of methylnitrosourea (mnu) to adult rats. the c6 glioma has been used extensively for a variety of studies, but since it arose in an outbred wistar rat, it is not syngeneic to any inbred strain, and its potential to evoke an alloimmune response is a serious limitation. the ...200919381449
piecing together the structure of retroviral integrase, an important target in aids therapy.integrase (in) is one of only three enzymes encoded in the genomes of all retroviruses, and is the one least characterized in structural terms. in catalyzes processing of the ends of a dna copy of the retroviral genome and its concerted insertion into the chromosome of the host cell. the protein consists of three domains, the central catalytic core domain flanked by the n-terminal and c-terminal domains, the latter being involved in dna binding. although the protein data bank contains a number o ...200919490099
comparison of metal-dependent catalysis by hiv-1 and asv integrase proteins using a new and rapid, moderate throughput assay for joining activity in solution.hiv-1 integrase (in) is an attractive target for the development of drugs to treat aids, and inhibitors of this viral enzyme are already in the clinic. nevertheless, there is a continuing need to devise new approaches to block the activity of this viral protein because of the emergence of resistant strains. to facilitate the biochemical analysis of wild-type in and its derivatives, and to measure the potency of prospective inhibitory compounds, a rapid, moderate throughput solution assay was dev ...200919563676
proviruses selected for high and stable expression of transduced genes accumulate in broadly transcribed genome areas.retroviruses and retrovirus-derived vectors integrate nonrandomly into the genomes of host cells with specific preferences for transcribed genes, gene-rich regions, and cpg islands. however, the genomic features that influence the transcriptional activities of integrated retroviruses or retroviral vectors are poorly understood. we report here the cloning and characterization of avian sarcoma virus integration sites from chicken tumors. growing progressively, dependent on high and stable expressi ...201020147411
transcription factor yy1 interacts with retroviral integrases and facilitates integration of moloney murine leukemia virus cdna into the host chromosomes.retroviral integrases associate during the early viral life cycle with preintegration complexes that catalyze the integration of reverse-transcribed viral cdna into the host chromosomes. several cellular and viral proteins have been reported to be incorporated in the preintegration complex. this study demonstrates that transcription factor yin yang 1 binds to moloney murine leukemia virus, human immunodeficiency virus type 1, and avian sarcoma virus integrases. the results of coimmunoprecipitati ...201020519390
architecture of a full-length retroviral integrase monomer and dimer, revealed by small angle x-ray scattering and chemical cross-linking.we determined the size and shape of full-length avian sarcoma virus (asv) integrase (in) monomers and dimers in solution using small angle x-ray scattering. the low resolution data obtained establish constraints for the relative arrangements of the three component domains in both forms. domain organization within the small angle x-ray envelopes was determined by combining available atomic resolution data for individual domains with results from cross-linking coupled with mass spectrometry. the f ...201121454648
retroviral integrases promote fraying of viral dna ends.in the initial step of integration, retroviral integrase (in) introduces precise nicks in the degenerate, short inverted repeats at the ends of linear viral dna. the scissile phosphodiester bond is located immediately 3' of a highly conserved ca/gt dinucleotide, usually two base pairs from the ends. these nicks create new recessed 3'-oh viral dna ends that are required for joining to host cell dna. previous studies have indicated that unpairing, "fraying," of the viral dna ends by in contributes ...201121622554
Localization of ASV Integrase-DNA Contacts by Site-Directed Crosslinking and their Structural Analysis.We applied crosslinking techniques as a first step in preparation of stable avian sarcoma virus (ASV) integrase (IN)-DNA complexes for crystallographic investigations. These results were then compared with the crystal structures of the prototype foamy virus (PFV) intasome and with published data for other retroviral IN proteins.201122145019
preparation of novel anti-ski monoclonal antibodies.ski is an avian sarcoma virus oncogene homolog best known for inhibiting tgf beta signaling through its association with the smad proteins. anti-ski antibodies (mabs) of high titer were prepared by immunizing balb/c mice with multifocal intradermal injections and fusing high titer antibody producing spleen cells with myeloma cells of sp2/0 origin. three mabs were selected for further characterization as classes and subclasses. antibodies were produced by these three clones with high affinities r ...201121851241
induction of some transformation-related properties by a transformation-defective mutant of avian sarcoma virus. 2003201095
a repetitive dna sequence in the salmonid fishes similar to a retroviral long terminal repeat.we describe the characteristics of a repetitive dna sequence from the rainbow trout and related salmonid fishes that is similar to a retroviral long terminal repeat (ltr). the repeat is 160 bp long and contains a region of homology to the ltr of the avian sarcoma virus. two clones with this repeat from the chum salmon also have a polypurine tract and trna binding site, respectively, and these clones may represent the two ltrs of a retrovirus or retroviral-like repetitive element. copies of the r ...20113133484
integration of avian sarcoma virus specific dna in mammalian chromatin. 2003169136
[characterization of the line of nonpermissive cells transformed by avian sarcoma virus b77 (author's transl)]. 1985214213
Displaying items 501 - 600 of 714