The product of the retroviral transforming gene v-myb is a truncated version of the protein encoded by the cellular oncogene c-myb

Klempnauer, K H; Ramsay, Gary; Bishop, J. Michael; Moscovici, Mișu; Moscovici, C.; McGrath, John P.; Levinson, Arthur D.

doi:10.1016/0092-8674(83)90416-6

Cited by 201 publications

(155 citation statements)

References 22 publications

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“…v-myb, the prototype member of the family, is the transforming gene of the E26 and AMV viruses that cause myeloblastosis in birds, and has been described as the truncated derivative of the cellular gene c-myb (Gonda and Bishop, 1983;Klempnauer et al, 1983). Myb proteins are conserved from the fruit¯y Drosophila melanogaster to vertebrates and presumably evolved from a primordial myb gene in a process of divergent evolution (Saville and Watson, 1988).…”

Section: Introductionmentioning

confidence: 99%

Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation

et al. 2000

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B-Myb is a transcription factor belonging to the myb family, whose activity has been associated with augmented DNA synthesis and cell cycle progression. We showed recently that B-Myb autoregulates its own expression through promoter transactivation. We report in this study that CDK9, the cyclin T associated kinase, which phosphorylates and activates RNA-Polymerase II, suppresses B-Myb autoregulation through direct interaction with the carboxyl-terminus of the B-Myb protein. Downregulation of the transactivating ability of B-Myb is independent of the kinase activity of CDK9, because a kinase de®cient mutant (dn-CDK9) also represses B-myb gene autoregulation. Overexpression of CDK9 did not result in suppression of p53-dependent transactivation or inhibition of the basal activity of the promoters tested so far, demonstrating that CDK9 is a B-Myb-speci®c repressor. Rather, transfection of the dominant negative dn-CDK9 construct inhibited the basal activity of the reporter genes, con®rming an essential role for CDK9 in gene transcription. In addition, Cyclin T1 restores B-Myb transactivating activity when co-transfected along with CDK9, suggesting that the down-regulatory e ect observed on B-Myb is speci®cally due to CDK9 alone. Thus, our data suggest that CDK9 is involved in the negative regulation of activated transcription mediated by certain transcription factors, such as B-Myb. This may indicate the existence of a feedback loop, mediated by the di erent activities of CDK9, which links basal with activated transcription.

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Section: Introductionmentioning

confidence: 99%

Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation

et al. 2000

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“…c-myb is the cellular progenitor of the avian retrovirus oncogene v-myb (Gonda and Bishop, 1983;Klempnauer et al, 1983). Unlike the other members of this family, B-myb is widely expressed.…”

Section: Introductionmentioning

confidence: 99%

The cell-cycle regulated transcription factor B-Myb is phosphorylated by Cyclin A/Cdk2 at sites that enhance its transactivation properties

Saville

Watson

1998

Oncogene

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Expression of the B-Myb transcription factor is upregulated during late G 1 phase of the cell cycle by an E2F-dependent transcriptional mechanism. B-Myb is speci®cally phosphorylated during S phase, suggesting that a cyclin-dependent kinase (Cdk) regulates its activity. Consistent with this notion, the S phase-speci®c cyclin A/Cdk2 was found previously to enhance B-Myb transactivation activity in cotransfected cells. In this study we provide evidence that B-Myb is a direct physiological target for cyclin A/Cdk2. We demonstrate that B-Myb is an in vitro substrate for cyclin A/Cdk2, but not for cyclin D1/Cdk4 or cyclin E/Cdk2. By mutating candidate Cdk2 phosphorylation sites, we show that B-Myb is phosphorylated at Thr447, Thr490, Thr497 and Ser581 by cyclin A/Cdk2 in vitro and that these sites are also phosphorylated in cycling U-2 OS cells. Inhibition of endogenous Cdk2 by dominant negative Cdk2 attenuated phosphorylation of Thr447, Thr490 and Thr497, but had no e ect upon Ser581 modi®cation. B-Myb transactivation activity was signi®cantly reduced in a mutant containing amino acid substitutions at all four identi®ed cyclin A/Cdk2 sites and was constitutively low in Saos-2 cells where endogenous cyclin A/Cdk2 activity was unable to phosphorylate ectopically expressed B-Myb. These data indicate that phosphorylation by cyclin A/Cdk2 is directly involved in enhancing B-Myb transactivation activity and that levels of endogenous cyclin A/Cdk2 activity may contribute to cell line-speci®c B-Myb function.

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“…The chicken cell lines BM2 (AMV-transformed myeloblasts), HD11 (MC29-transformed macrophages) and HD3 (AEV-transformed erythroblasts) have been described (Klempnauer et al, 1983;Burk and Klempnauer, 1993). 10.4 is a derivative of the HD11 cell line expressing a vMyb/ER fusion protein (Burk and Klempnauer, 1991).…”

Section: Cell Linesmentioning

confidence: 99%

“…v-myb is a structurally altered version of the chicken c-myb gene and has su ered Nand C-terminal truncations as well as point mutations during retroviral transduction (Klempnauer et al, 1982(Klempnauer et al, , 1983. A large body of evidence indicates that the c-myb gene controls the proliferation and differentiation of hematopoietic precursor cells and that it is essential for the development of the hematopoietic system.…”

Section: Introductionmentioning

confidence: 99%

The chicken adenosine receptor 2B gene is regulated by v-myb

1997

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The product of the retroviral transforming gene v-myb is a truncated version of the protein encoded by the cellular oncogene c-myb

Cited by 201 publications

References 22 publications

Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation

Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation

The cell-cycle regulated transcription factor B-Myb is phosphorylated by Cyclin A/Cdk2 at sites that enhance its transactivation properties

The chicken adenosine receptor 2B gene is regulated by v-myb

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