Article abstract
Nature Cell Biology 9, 1253 - 1262 (2007)
Published online: 14 October 2007 | doi:10.1038/ncb1645
There is a Corrigendum (December 2007) associated with this Article.
SIRT1 sumoylation regulates its deacetylase activity and cellular response to genotoxic stress
Yonghua Yang1,6, Wei Fu1, Jiandong Chen2,3, Nancy Olashaw2,3, Xiaohong Zhang1,2,3, Santo V. Nicosia1,2,4, Kapil Bhalla5 & Wenlong Bai1,2,3
Abstract
SIRT1 is the closest mammalian homologue of yeast SIR2, an important ageing regulator that prolongs lifespan in response to caloric restriction. Despite its importance, the mechanisms that regulate SIRT1 activity are unclear. Our study identifies a novel post-translational modification of SIRT1, namely sumoylation at Lys 734. In vitro sumoylation of SIRT1 increased its deacetylase activity. Conversely, mutation of SIRT1 at Lys 734 or desumoylation by SENP1, a nuclear desumoylase, reduced its deacetylase activity. Stress-inducing agents promoted the association of SIRT1 with SENP1 and cells depleted of SENP1 (but not of SENP1 and SIRT1) were more resistant to stress-induced apoptosis than control cells. We suggest that stress-inducing agents counteract the anti-apoptotic activity of SIRT1 by recruiting SENP1 to SIRT1, which results in the desumoylation and inactivation of SIRT1 and the consequent acetylation and activation of apoptotic proteins.
- Departments of Pathology and Cell Biology, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, Florida 33612–4799, USA.
- Department of Interdisciplinary Oncology, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, Florida 33612–4799, USA.
- Program of Molecular Oncology, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
- Program of Experimental Therapeutics, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
- Medical College of Georgia Cancer Center, 1120 15th Street, CN2101A, Augusta, GA 30912, USA.
- Current address: Medical College of Georgia Cancer Center, 1120 15th Street, CN2101A, Augusta, GA 30912, USA.
Correspondence to: Wenlong Bai1,2,3 e-mail: wbai@health.usf.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylationOncogene Original Article
Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylationOncogene Original Article
The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylaseThe EMBO Journal Article (03 Jun 2002)
See all 67 matches for Research
