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.
Original language | English (US) |
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Pages (from-to) | 1171-1178 |
Number of pages | 8 |
Journal | Nature cell biology |
Volume | 8 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2006 |
ASJC Scopus subject areas
- Cell Biology