| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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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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