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modulation of c-myb-induced transcription activation by a phosphorylation site near the negative regulatory domain.the c-myb protooncogene encodes a highly conserved transcription factor that functions as both an activator and a repressor of transcription. the v-myb oncogenes of e26 leukemia virus and avian myeloblastosis virus encode proteins that are truncated at both the amino and the carboxyl terminus, deleting portions of the c-myb dna-binding and negative regulatory domains. this has led to speculation that the deleted regions contain important regulatory sequences. we previously reported that the 42-k ...19957604007
mutations in the dna-binding and transcriptional activation domains of v-myb cooperate in transformation.the v-myb protein encoded by avian myeloblastosis virus causes oncogenic transformation of monoblastic cells committed to the monocyte/macrophage lineage. v-myb is a doubly truncated form of its normal cellular counterpart, c-myb. in addition to its n- and c-terminal deletions, v-myb contains a number of amino acid substitutions relative to c-myb. we have previously shown that neither overexpression of c-myb nor introduction of these amino acid substitutions into c-myb is sufficient for transfor ...19957884901
avian myeloblastic cell lines transformed by two nuclear oncoproteins, p135gag-myb-ets and p61/63myc: a model of retinoic acid-induced differentiation not abrogated by v-erba.we previously demonstrated that the retroviral construct mhe226 transducing both the p135gag-myb-ets and p61/63myc nuclear proteins induces solid hemopoietic tumors in early chicken embryos. in the present paper, we report the characterization of two mhe226-transformed cell lines established from such hemopoietic tumors retrieved from the heart of a 13-day embryo. cytological analysis indicated a myeloblastic phenotype. these mhe226 cell lines were positive for the mep17 monoclonal antibody but ...19947986751
translation of avian myeloblastosis virus genomic rna in vitro.defective viral particles (dvp) were isolated from the medium of chicken myeloblasts transformed by avian myeloblastosis virus (amv) in the absence of helper viruses (non-producer myeloblasts). a 60s genomic rna complex of amv was isolated from dvp and translated in vitro. the predominant translation product was the gag polyprotein precursor pr76gag.19938105660
a novel multilineage cell-surface antigen expressed on terminally differentiated chicken b cells in mucosal tissues.a murine monoclonal antibody, 5m19, produced to a cell line transformed by an avian myeloblastosis virus, detects an antigen, designated chl5, that is expressed on multiple lineages of hematopoietic cells from noninfected chickens. immunochemical analysis demonstrated the chl5 antigen to be a homodimer of two disulfide-bonded chains each having an apparent molecular weight of 128,000. the highest level of expression was found on myelomonocytic cells, including granulocytes, monocytes, and macrop ...19948131206
transformation of myelomonocytic cells by the avian myeloblastosis virus is determined by the v-myb oncogene, not by the unique long terminal repeats of the virus.the avian myeloblastosis virus (amv) induces acute monoblastic leukemia in chickens and transforms only myelomonocytic cells in vitro. the long terminal repeat (ltr) regulatory region of amv is unique among the known classes of avian retrovirus ltrs. we demonstrate that the substitution of the amv ltrs by rous sarcoma virus ltrs did not alter the cell type specificity or the transforming ability of the virus.19948139052
avian myeloblastosis virus core-bound 7 s dna, a collection of minute replicative host-cell dna structures.the early replicative nature of avian myeloblastosis virus core-bound 7 s dna (amv dna), indicated by our preceding findings (ríman et al., 1993), has been confirmed using various experimental approaches. it has been shown by agarose and polyacrylamide gel electrophoresis that this dna represents actually a collection of molecules the size of which is strongly reminiscent of the minute early replicative structures found in dna of sea urchin embryos (baldari et al., 1978). with such a characteris ...19938184786
synergistic activation of the chicken mim-1 gene by v-myb and c/ebp transcription factors.the retroviral oncogene v-myb encodes a transcriptional activator which is responsible for the activation of the mim-1 gene in myelomonocytic cells transformed by v-myb. the mim-1 promoter contains several myb consensus binding sites and has previously been shown to be regulated directly by v-myb. here we report that the mim-1 gene is activated synergistically by v-myb and different c/ebp transcription factors. we have cloned a chicken c/ebp-related gene that is highly expressed in myeloid cells ...19938491193
the noncoding and surface envelope coding sequences of myeloblastosis-associated virus are respectively responsible for nephroblastoma development and renal hyperplasia.the use of chimeric viruses allowed us to establish that myeloblastosis-associated virus long terminal repeat sequences are necessary and sufficient for induction of nephroblastoma in chickens and that the blastemal hyperplasia induced by env su is not a prerequisite for tumor development but rather constitutes a predisposing stage.19968642688
faetl motif required for leukemic transformation by v-myb.the nuclear protein v-myb, encoded by the avian myeloblastosis virus (amv), can induce acute monoblastic leukemia in vivo and transform chicken myelomonocytic cells in culture. the n terminus of v-myb functions as the dna-binding domain, and multiple central and c-terminal regions of this protein have been reported to function in transcriptional activation of model reporter genes. we showed previously that a c-terminal domain (amino acids 296 to 371) is required for transcriptional activation an ...19968764074
t-cell lymphomas in v-myb transgenic mice.v-myb, the transforming protein of avian myeloblastosis virus, causes acute myeloid leukemia in chickens. similarly, truncation and rearrangement of the c-myb proto-oncogene to yield a v-myb-like protein leads to myeloid and b cell lymphomas in chickens and mice, and may be a factor in a number of human cancers. to study the effects of deregulation of v-myb on t cell development, we have generated lines of transgenic mice in which the v-myb oncoprotein is expressed in a t-cell-specific fashion. ...19968950988
constitutive expression of full-length c-myb transforms avian cells characteristic of both the monocytic and granulocytic lineages.both viral myb (v-myb) and cellular myb (c-myb) are nuclear sequence-specific dna-binding proteins that can function as transcriptional activators. v-myb, encoded by avian myeloblastosis virus, induces acute monoblastic leukemia in chickens and transforms avian myelomonocytic cells in culture. the normal c-myb protein is essential for hematopoietic development. previous reports suggested that truncation of c-myb is required for oncogenic transformation of avian myelomonocytic cells in culture. i ...19978993832
oncogenic point mutations induce altered conformation, redox sensitivity, and dna binding in the minimal dna binding domain of avian myeloblastosis virus v-myb.c-myb is the founder member of a class of transcription factors with tryptophan-rich repeats responsible for dna binding. activated oncogenic forms of myb are encoded by the avian retroviruses, avian myeloblastosis virus (amv) and e26. amv v-myb encodes a truncated protein with 11 point mutations relative to c-myb. the mutations in the dna binding domain (dbd) were reported to impose distinct phenotypes of differentiation on transformed myeloid cells (introna, m., golay, j., frampton, j., nakano ...19979020167
micromorphology of cytoplasmic nucleoprotein complexes harboring an extrachromosomal dna closely related to avian myeloblastosis virus core-bound dna.nucleoprotein (np) complexes constituting the three basic components (a, b, c) of the postmicrosomal sediment (poms) of chicken leukemic myeloblasts (chlms) which contain extrachromosomal dna closely related to avian myeloblastosis virus dna were analyzed electron microscopically. it was shown that these np complexes resemble micromorphologically, depending on the origin of their poms components, np structures involved in three successive stages of early dna synthesis. nucleic acids harbored in ...19979315726
nucleoprotein complexes harboring an extrachromosomal dna closely related to 7 s dna of avian myeloblastosis virus: physico-chemical properties and representation of nucleic acids.the source of avian myeloblastosis virus (amv) dna, an extrachromosomal small polydisperse dna, present in the material forming the postmicrosomal sediment (poms) of lysed chicken leukemic myeloblasts (chlms) is organized into nucleoprotein (np) complexes containing always rna. this material, radioactively double-labelled for dna and rna, separated in isopycnic sucrose gradients into three poms components (a,b,c) differing from one another in properties of labelling for dna and rna, sucrose dens ...19979391649
transformation by v-myb.the v-myb oncogene of the avian myeloblastosis virus (amv) is unique among known oncogenes in that it causes only acute leukemia in animals and transforms only hematopoietic cells in culture. amv was discovered in the 1930s as a virus that caused a disease in chickens that is similar to acute myelogenous leukemia in humans (hall et al., 1941). this avian retrovirus played an important role in the history of cancer research for two reasons. first, amv was used to demonstrate that all oncogenic vi ...199910378700
retinoid x receptor suppresses transformation by the v-myb oncogene.the v-myb oncogene of avian myeloblastosis virus causes acute monoblastic leukemia in vivo and transforms myelomonocytic cells in culture. retinoids are potent regulators of proliferation and differentiation in various cell types, and they can initiate differentiation in certain types of leukemic cells. however, the bm2 v-myb-transformed chicken monoblastic cell line is resistant to retinoic acid treatment. we found that overexpression of the retinoid x receptor confers sensitivity of bm2 cells ...199910614788
the "small" polydisperse cytoplasmic extrachromosomal dna of chicken leukaemic myeloblasts and the avian myeloblastosis virus core-bound dna seem to descend from origin regions of chromosomal dna replication.nucleotide sequences are presented for 12, 7 and 12 cloned extrachromosomal dnas by nature harbored in nucleoprotein (np) complexes forming chicken leukaemic myeloblast (chlm) post microsomal sediment (poms) components a, b and c, respectively, and for 11 cloned avian myeloblastosis virus (amv) dnas. analysis of the abundance of sequence motifs significant for eukaryotic chromosomal dna replication origin (ori) regions (and their initiation zones) has shown that these dnas are reminiscent of cel ...199910672338
the chicken pdcd4 gene is regulated by v-myb.the retroviral oncogene v-myb encodes a transcription factor (v-myb) which is responsible for the ability of avian myeloblastosis virus (amv) to transform myelomonocytic cells. v-myb is thought to disrupt the differentiation of myelomonocytic cells by affecting the expression of specific target genes. to identify such genes we have analysed the gene expression in a myelomonocytic chicken cell line that carries an estrogen inducible version of v-myb by differential display. here we describe the i ...200111313950
ori-somes, nucleoprotein complexes descending from origin regions of animal chromosomal dna replication. a micromorphological study.micromorphology of nucleoprotein (np) complexes designated according to their descent and shape as ori-somes is presented. these np complexes of three different types harbor molecules of cytoplasmic "small" polydisperse dna, which descend from origin regions of chromosomal dna replication and are equipped, as shown previously, with early dna-synthesizing activities. by negative staining the ori-somes are visualized as particles of irregular shape, sometimes of a subunit-like structure. micromorp ...200111697738
mechanism of c-myb-c/ebp beta cooperation from separated sites on a promoter.c-myb, but not avian myeloblastosis virus (amv) v-myb, cooperates with c/ebp beta to regulate transcription of myeloid-specific genes. to assess the structural basis for that difference, we determined the crystal structures of complexes comprised of the c-myb or amv v-myb dna-binding domain (dbd), the c/ebp beta dbd, and a promoter dna fragment. within the c-myb complex, a dna-bound c/ebp beta interacts with r2 of c-myb bound to a different dna fragment; point mutations in v-myb r2 eliminate suc ...200211792321
e26 leukemia virus converts primitive erythroid cells into cycling multilineage progenitors.acute chicken leukemia retroviruses, because of their capacity to readily transform hematopoietic cells in vitro, are ideal models to study the mechanisms governing the cell-type specificity of oncoproteins. here we analyzed the transformation specificity of 2 acute chicken leukemia retroviruses, the myb-ets- encoding e26 virus and the erba/erbb-encoding avian erythroblastosis virus (aev). while cells transformed by e26 are multipotent (designated "mep" cells), those transformed by aev resemble ...200312393697
phosphorylation-dependent down-regulation of c-myb dna binding is abrogated by a point mutation in the v-myb oncogene.the viral myb (v-myb) oncoprotein of the avian myeloblastosis virus (amv) is an activated form of the cellular transcription factor c-myb causing acute monoblastic leukemia in chicken. oncogenic v-myb alterations include n- and c-terminal deletions as well as point mutations. whereas truncations in myb cause loss of various protein modifications, none of the point mutations in v-myb has been directly linked to protein modifications. here we show that the dna-binding domain of c-myb can be phosph ...200312456674
differential effects of v-jun and c-jun proteins on v-myb-transformed monoblasts.the v-myb oncogene of avian myeloblastosis virus transforms myelomonocytic cells in vitro. the line of v-myb-transformed chicken monoblasts bm2 can be induced to terminal differentiation using phorbol esters. the fact that jun proteins are up-regulated in the phorbol ester-treated bm2 cells prompted us to investigate the role of the jun proteins in regulation of myeloid differentiation. we ectopically expressed v-jun and c-jun in bm2 cells and evaluated their effects on differentiation and proli ...200212475180
trichostatin a suppresses transformation by the v-myb oncogene in bm2 cells.bm2 cells are chicken monoblasts transformed by the v-myb oncogene of avian myeloblastosis virus. the constitutively high v-myb expression interferes with the terminal differentiation of bm2 cells, but these cells can be induced to differentiate into macrophage-like cells by phorbol esters. histone acetylation plays an important role in regulation of transcription and is particularly relevant to the regulation and pathology of hematopoiesis. in the present study, we examined the contribution of ...200312804181
v-myb mediates cooperation of a cell-specific enhancer with the mim-1 promoter.the oncogenic transcription factor v-myb disrupts myelomonocytic differentiation and transforms myelomonocytic cells by deregulating the expression of specific target genes. one of these genes, the chicken mim-1 gene, is activated by myb exclusively in myelomonocytic cells and, therefore, has been an interesting model system to study how myb activates a target in a lineage-specific manner. previous work has suggested that myb activates mim-1 by cooperating with ccaat box/enhancer binding protein ...200515601869
cbp sensitizes v-myb-transformed monoblasts to differentiation inducers.creb-binding protein (cbp) regulates gene expression by binding to certain components of basal transcription machinery and by histone acetylation. in addition, it integrates various cellular signaling pathways through binding to multiple transcription factors, including the myb proteins. we report in this study that cbp can partially suppress function of the v-myb oncoprotein in leukemic cells. although originally described as an activator of v-myb function, we show that cbp can also act as a v- ...200516026544
identification of potential human oncogenes by mapping the common viral integration sites in avian nephroblastoma.gene deregulation is a frequent cause of malignant transformation. alteration of the gene structure and/or expression leading to cellular transformation and tumor growth can be experimentally achieved by insertion of the retroviral genome into the host dna. retrovirus-containing host loci found repeatedly in clonal tumors are called common viral integration sites (cvis). cvis are located in genes or chromosomal regions whose alterations participate in cellular transformation. here, we present th ...200616397219
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
the promoter regions of the myb-regulated adora2b and mcm4 genes co-localize with origins of dna replication.the retroviral oncogene v-myb encodes a transcription factor (v-myb) which is responsible for the transformation of myelomonocytic cells by avian myeloblastosis virus (amv). v-myb is thought to exert its biological effects by deregulating the expression of specific target genes. we have recently demonstrated that the chicken gas41 gene, whose promoter co-localizes with an origin of dna replication, is a bona fide myb target gene. because of this finding we have asked whether other myb-regulated ...200717822556
a dual activation mechanism for myb-responsive genes in myelomonocytic cells.the retroviral oncogene v-myb encodes a transcription factor (v-myb) which is responsible for the transformation of myelomonocytic cells by avian myeloblastosis virus (amv). v-myb is thought to exert its biological effects by deregulating the expression of specific target genes. here we have used dnasei hypersensitive site mapping and reporter gene assays to study the activation of three myb target genes--mim-1, the lysozyme gene and the c/ebpbeta gene--all of which are activated by myb in myelo ...200817950008
oncogenic point mutations in the myb dna-binding domain alter the dna-binding properties of myb at a physiological target gene.the oncoprotein v-myb of avian myeloblastosis virus (amv) transforms myelomonocytic cells by deregulating specific target genes. previous work has shown that the oncogenic potential of v-myb was activated by truncation of n- and c-terminal sequences of c-myb and was further increased by amino acid substitutions in the dna-binding domain and other parts of the protein. we have analyzed the activation of the chicken lysozyme gene which is strongly activated by c-myb but not by its oncogenic counte ...200717959653
in vitro transformation with avian myelocytomatosis virus strain cmii: characterization of the virus and its target cells.avian myelocytomatosis virus strain cmii induced an in vitro transformation in cells from various hematopoietic tissues and could be quantitated by focus and soft agar colony assay techniques. the cmii-transformed bone marrow cells had a high proliferative capacity in comparison to uninfected controls. the cells closely resembled hematopoietic cells transformed by strain mc29 myelocytomatosis virus, but differed from avian myeloblastosis virus (amv)-transformed cells. they were phagocytic, becam ...197718625478
the use of elisa for detection of exogenous and endogenous avian leukosis viral antigens in basic breeding flocks.an enzyme-linked immunosorbent assay (elisa) for avian leukosis/ sarcoma virus (alv) group-specific (gs) antigens was used to study the identification of hens which congenitally excrete exogenous alv. the sensitivity of this assay was compared with that of the phenotypic mixing test (pmt) and the direct complement fixation test (cft) by testing limiting dilutions of purified avian myeloblastosis virus (amv), embryo homogenates and albumens. about 0.4 ng/ml of purified amv protein could be detect ...198318766804
myb-induced chromatin remodeling at a dual enhancer/promoter element involves non-coding rna transcription and is disrupted by oncogenic mutations of v-myb.the oncogene v-myb of avian myeloblastosis virus (amv) encodes a transcription factor (v-myb) that transforms myelomonocytic cells by deregulating the expression of specific target genes. v-myb has acquired its oncogenic potential by truncation as well as by a number of point mutations of its cellular progenitor c-myb. as a result of these changes, the target gene spectrum v-myb differs from that of c-myb. we recently showed that the chicken mim-1 gene, a c-myb target gene that is not activated ...200919841477
myb proteins talking to their dna (review).dna sequence-specific proteins called transcription factors found in all multicellular organisms control the expression of genes and are involved in the regulation of the cell cycle. myb oncoproteins are transcription factors with a distinct dna binding domain lacking zinc fingers or a basic region. found originally in the avian myeloblastosis virus (v-myb), then in the genome of chickens (c-myb), the dna binding domain of myb occurs in regulatory proteins from mammals including humans, plants, ...199421559564
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