Toggle Main Menu Toggle Search

Open Access padlockePrints

SIRT1 negatively regulates HDAC1-dependent transcriptional repression by the RBP1 family of proteins

Lookup NU author(s): Dr Olivier Binda


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Both RBP1 and the highly related protein BCAA play a role in the induction of growth arrest and cellular senescence via mechanisms involving transcriptional repression. While investigating the transcriptional repression activities of RBP1, we observed a genetic link between RBP1 and SIR2. Further work uncovered an interaction between RBP1 family proteins and the mammalian homologue of SIR2, SIRT1. Interestingly, the HDAC-dependent transcriptional repression domain of RBP1 proteins, termed R2, is necessary and sufficient for the interaction with SIRT1. In vitro and in vivo binding studies indicated that the p33(ING1b) and p33(ING2) subunits of the mSIN3A/HDAC1 complex are responsible for the recruitment of SIRT1 to the R2 domain. To investigate the biological relevance of this interaction, we used the sirtuin activator resveratrol and the sirtuin inhibitor sirtinol in transcriptional repression assays and demonstrated that SIRT1 activity negatively regulates R2-mediated transcriptional repression activity. We therefore propose a novel mechanism of class I HDAC regulation by a class III HDAC. Explicitly, SIRT1 is recruited by ING proteins and inhibits R2-associated mSIN3A/HDAC1 transcriptional repression activity.

Publication metadata

Author(s): Binda O, Nassif C, Branton PE

Publication type: Article

Publication status: Published

Journal: Oncogene

Year: 2008

Volume: 27

Issue: 24

Pages: 3384-3392

ISSN (print): 0950-9232

ISSN (electronic): 1476-5594

Publisher: Nature Publishing Group


DOI: 10.1038/sj.onc.1211014

PubMed id: 18193082


Altmetrics provided by Altmetric