Volume 21, No 5, May 2011

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 21 Issue 5, May 2011: 807-816

ORIGINAL ARTICLES

Regulation of REGγ cellular distribution and function by SUMO modification

Yan Wu^1,*, Lu Wang^1,*, Ping Zhou¹, Guangqiang Wang¹, Yu Zeng¹, Ying Wang¹, Jian Liu^1,3, Bianhong Zhang¹, Shuang Liu¹, Honglin Luo² and Xiaotao Li^1,3

¹Institute of Biomedical Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China

²The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia-St Paul's Hospital, 1081 Burrard Street, Vancouver, Canada V6Z 1Y6

³Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Correspondence: Xiaotao Li,(xiaotaol@bcm.edu)

Discovery of emerging REGγ-regulated proteins has accentuated the REGγ-proteasome as an important pathway in multiple biological processes, including cell growth, cell cycle regulation, and apoptosis. However, little is known about the regulation of the REGγ-proteasome pathway. Here we demonstrate that REGγ can be SUMOylated in vitro and in vivo by SUMO-1, SUMO-2, and SUMO-3. The SUMO-E3 protein inhibitor of activated STAT (PIAS)1 physically associates with REGγ and promotes SUMOylation of REGγ. SUMOylation of REGγ was found to occur at multiple sites, including K6, K14, and K12. Mutation analysis indicated that these SUMO sites simultaneously contributed to the SUMOylation status of REGγ in cells. Posttranslational modification of REGγ by SUMO conjugation was revealed to mediate cytosolic translocation of REGγ and to cause increased stability of this proteasome activator. SUMOylation-deficient REGγ displayed attenuated ability to degrade p21^Waf//Cip1 due to reduced affinity of the REGγ SUMOylation-defective mutant for p21. Taken together, we report a previously unrecognized mechanism regulating the activity of the proteasome activator REGγ. This regulatory mechanism may enable REGγ to function as a more potent factor in protein degradation with a broader substrate spectrum.

Cell Research (2011) 21:807-816. doi:10.1038/cr.2011.57; published online 29 March 2011

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