2004 Fiscal Year Final Research Report Summary
Analysis of c-Myb dependent transcriptional repression mechanism by Ski
| Project/Area Number |
15570151
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | RIKEN |
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Principal Investigator |
NOMURA Teruaki RIKEN, Molecular Genetics Laboratory, Senior Research Scientist, 石井分子遺伝学研究室, 先任研究員 (80231512)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Myb / Ski / Corepressor |
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| Research Abstract |
In this study, we got the several important data about the regulation of transcriptional activities of c-Myb. TIF1β directly binds to the C-terminus negative regulatory domain and other three corepressors, Ski, N-CoR and mSin3A bind to the DNA binding domain of c-Myb. These corepressors recruit the histon deacetylase to c-Myb and negatively regulate c-Myb dependent trans-activation. Furthermore there was the genetic interaction between the Drosophila TIF1β homologue, Bonus and Drosophila Myb in vivo. The corepressor Ski competes with the coactivator CBP for binding to c-Myb, suggesting the role of Ski in the switching mechanism of positive and negative transcriptional activities of c-Myb. V-Myb has the reduced affinities with the corepressors and the enhanced transcriptional activities compare to the c-Myb. It was also found that c-Myb bound to Hipk2(homeodomain-interacting protein kinase 2). Hipk2 is regulated by Wnt-1 signaling pathway. When Wnt-1bind to Frizzled receptors, TAK1(TGFβ-activated-kinase 1), Hipk2,and NLK(nemo-like kinase) are activated, which results in the phosphorylation of c-Myb at multiple sites. It induces ubiquitination and proteasome-dependent degradation of c-Myb. V-Myb was relatively resistant to Wnt-1 induced protein degradation, which is suggesting the higher oncogenic activity of v-Myb.
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Research Products
(12 results)
