Oncogenic Activation of c-Myb Correlates with a Loss of Negative Regulation by TIF1β and Ski
| Autor: | Hiroki Ito, Matiullah Khan, Jun Tanikawa, Emi Ichikawa-Iwata, Shunsuke Ishii, Hiroshi Akimaru, Teruaki Nomura, Chie Kanei-Ishii |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Transcriptional Activation
animal structures Genes myb Tripartite Motif-Containing Protein 28 Biology Biochemistry Mice Transcription (biology) Proto-Oncogene Proteins Coactivator Animals MYB Molecular Biology Gene Oncogene fungi Nuclear Proteins Cell Biology Molecular biology DNA-Binding Proteins Gene Expression Regulation Neoplastic Repressor Proteins Haematopoiesis Mutation Histone deacetylase complex Drosophila Corepressor Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 279:16715-16726 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m313069200 |
| Popis: | The c-myb proto-oncogene product (c-Myb) regulates proliferation of hematopoietic cells by inducing the transcription of a group of target genes. Removal or mutations of the negative regulatory domain (NRD) in the C-terminal half of c-Myb leads to increased transactivating capacity and oncogenic activation. Here we report that TIF1beta directly binds to the NRD and negatively regulates the c-Myb-dependent trans-activation. In addition, three corepressors (Ski, N-CoR, and mSin3A) bind to the DNA-binding domain of c-Myb together with TIF1beta and recruit the histone deacetylase complex to c-Myb. Furthermore, the Drosophila TIF1beta homolog, Bonus, negatively regulates Drosophila Myb activity. The Ski corepressor competes with the coactivator CBP for binding to c-Myb, indicating that the selection of coactivators and corepressors is a key event for c-Myb-dependent transcription. Mutations or deletion of the NRD of c-Myb and the mutations found in the DNA-binding domain of v-Myb decrease the interaction with these corepressors and weaken the corepressor-induced negative regulation of Myb activity. These observations have conceptual implications for understanding how the nuclear oncogene is activated. |
| Databáze: | OpenAIRE |
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