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MM-1 facilitates degradation of c-Myc by recruiting proteasome and a novel ubiquitin E3 ligase.
| Title: | MM-1 facilitates degradation of c-Myc by recruiting proteasome and a novel ubiquitin E3 ligase. |
| Authors: | Kimura, Yumiko Browse this author | | Nagao, Arisa Browse this author | | Fujioka, Yuko Browse this author | | Satou, Akiko Browse this author | | Taira, Takahiro Browse this author →KAKEN DB | | Iguchi-Ariga, Sanae M M Browse this author →KAKEN DB | | Ariga, Hiroyoshi Browse this author →KAKEN DB |
| Keywords: | c-Myc | | MM-1 | | degradation | | ubiquitin-proteasome system |
| Issue Date: | Oct-2007 |
| Publisher: | D.A. Spandidos |
| Journal Title: | International journal of oncology |
| Volume: | 31 |
| Issue: | 4 |
| Start Page: | 829 |
| End Page: | 836 |
| PMID: | 17786314 |
| Abstract: | We have reported that a novel c-Myc-binding protein, MM-1, repressed the E-box-dependent transcription activity of c-Myc by recruiting the HDAC1 complex via TIF1beta/KAP1, a transcriptional corepressor. We have also reported that a mutation of A157R in MM-1, which is often observed in patients with leukemia or lymphoma, abrogated all of the repressive activities of MM-1 toward c-Myc, indicating that MM-1 is a novel tumor suppressor. In this study, we found that MM-1 was bound to a component of proteasome and stimulated degradation of c-Myc in human cells. Knockdown of endogenous MM-1 in human HeLa cells by introduction of siRNA against MM-1 stabilized the endogenous c-Myc. To identify proteins that participate in c-Myc degradation by MM-1, in vivo and in vitro binding assays were carried out. The results showed that MM-1 directly bound to Rpt3, a subunit of 26S proteasome, and that c-Myc directly bound to Skp2, which recruited ElonginC, ElonginB and Cullin2, thereby forming a novel ubiquitin E3 ligase. Knockdown of endogenous Cullin2 stabilized the endogenous c-Myc. Thus, MM-1 is a factor that connects c-Myc to the ubiquitin E3 ligase and the proteasome. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/53727 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 有賀 寛芳
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