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- Title
Neddylation of a breast cancer-associated protein recruits a class III histone deacetylase that represses NFκB-dependent transcription.
- Authors
Gao, Fei; Cheng, Jinke; Shi, Tong; Yeh, Edward T. H.
- Abstract
Neddylation has an important role in ubiquitin-mediated protein degradation through modification of cullins, which are the main substrates for NEDD8 modification. Here, we show that breast cancer–associated protein 3 (BCA3) is a NEDD8 substrate. BCA3 suppressed NFκB-dependent transcription through its ability to bind to p65 and the cyclin D1 promoter in a neddylation-dependent manner. Transcriptional suppression mediated by BCA3 may be attributed to the ability of neddylated BCA3 to recruit SIRT1, a class III histone deacetylase. Silencing of endogenous BCA3 in DU145 and MCF7 cells enhanced NFκB transcription and inhibited tumour necrosis factor (TNF)α-induced apoptosis. Conversely, BCA3 silencing could be reversed by over-expression of wild-type BCA3 and SENP8, a NEDD8-specific protease, but not by neddylation-deficient BCA3 or a SENP8 mutant. These results provide a crucial link between neddylation and transcriptional regulation by SIRT1, a NAD-dependent histone deacetylase that prolongs life span in yeast and worms.
- Subjects
BACTERIAL conjugation; GENETICS of breast cancer; UBIQUITIN; HISTONE deacetylase; TUMOR suppressor proteins; TUMOR necrosis factors; APOPTOSIS
- Publication
Nature Cell Biology, 2006, Vol 8, Issue 10, p1171
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb1483