期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 21, 期 8, 页码 2918-2932出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.21.8.2918-2932.2001
关键词
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资金
- NIGMS NIH HHS [GM485180] Funding Source: Medline
Retinoblastoma (RE) tumor suppressor family pocket proteins induce cell cycle arrest by repressing transcription of E2F-regulated genes through both histone deacetylase (HDAC)-dependent and -independent mechanisms. In this study we have identified a stable complex that accounts for the recruitment of both repression activities to the pocket. One component of this complex is REP1, a known pocket-binding protein that exhibits both HDAC-dependent and -independent repression functions. RE family proteins were shown to associate via the pocket with previously identified mSIN3-SAP30-HDAC complexes containing exclusively class I HDACs. Such enzymes do not interact directly with RE family proteins but rather utilize RBP1 to target the pocket. This mechanism was shown to account for the majority of RE-associated HDAC activity. We also show that in quiescent normal human cells this entire RBP1-mSIN3-SAP30-HDAC complex colocalizes with both RE family members and E2F4 in a limited number of discrete regions of the nucleus that in other studies have been shown to represent the initial origins of DNA replication following growth stimulation. These results suggest that RE family members, at least in part, drive exit from the cell cycle by recruitment of this HDAC complex via REP1 to repress transcription from E2F-dependent promoters and possibly to alter chromatin structure at DNA origins.
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