| First Author | Chini CC | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 52 | Pages | 40830-7 |
| PubMed ID | 21030595 | Mgi Jnum | J:221556 |
| Mgi Id | MGI:5640947 | Doi | 10.1074/jbc.M110.153270 |
| Citation | Chini CC, et al. (2010) HDAC3 is negatively regulated by the nuclear protein DBC1. J Biol Chem 285(52):40830-7 |
| abstractText | HDAC3 is a member of the class I histone deacetylase family that regulates gene expression by deacetylation of histones and non-histone proteins. HDAC3 activity has been shown to be modulated by interaction with the co-repressors NCoR and SMRT. Here, we present evidence that the nuclear protein DBC1 is an endogenous inhibitor of HDAC3. DBC1 has been previously identified as a regulator of some nuclear receptors, the methyltransferase SUV39H1, and the NAD-dependent deacetylase SIRT1. Furthermore, DBC1 has been shown to influence transcription regulation and apoptosis, and it may also act as a tumor suppressor. We found that DBC1 interacts and specifically inhibits the deacetylase HDAC3. This interaction depends on the N terminus of DBC1 and the C terminus of HDAC3. Expression of DBC1 not only inhibited HDAC3 activity but also altered its subcellular distribution. In addition, knockdown of endogenous DBC1 in cells and knock-out in mouse tissues increased HDAC3 deacetylase activity. Together, these results identify DBC1 as a new regulator of HDAC3 and demonstrate that DBC1 is a negative regulator of two key distinct deacetylases, SIRT1 and HDAC3. These findings may lead to a better understanding of the biological roles of DBC1 and HDAC3 in metabolic diseases and cancer. |
