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Molecular and Cellular Biology, July 2004, p. 6021-6028, Vol. 24, No. 13
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.13.6021-6028.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

SENP1 Enhances Androgen Receptor-Dependent Transcription through Desumoylation of Histone Deacetylase 1

Jinke Cheng,1,2 Dachun Wang,1,2 Zhengxin Wang,3 and Edward T. H. Yeh1,2*

Department of Cardiology,1 Department of Cancer Biology, The University of Texas-M. D. Anderson Cancer Center,3 Research Center for Cardiovascular Diseases, Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas-Houston Health Science Center, Houston, Texas 770302

Received 7 March 2004/ Returned for modification 30 March 2004/ Accepted 14 April 2004

SUMO (also called Sentrin) is a ubiquitin-like protein that plays an important role in regulating protein function and localization. It is known that several nuclear receptors are modified by SUMO; however, the effect of desumoylation in regulating nuclear receptor function has not been elucidated. Here we show that androgen receptor (AR)-mediated transcription is markedly enhanced by SENP1, a member of SUMO-specific protease family. SENP1's ability to enhance AR-dependent transcription is not mediated through desumoylation of AR, but rather through its ability to deconjugate histone deacetylase 1 (HDAC1), thereby reducing its deacetylase activity. HDAC1's repressive effect on AR-dependent transcription could be reversed by SENP1 and by deletion of its sumoylation sites. RNA interference depletion of endogenous HDAC1 also reduced SENP1's effect. Thus, SENP1 could regulate AR-dependent transcription through desumoylation of HDAC1. These studies provide insights on the potential role of desumoylation in the regulation of nuclear receptor activity.

* Corresponding author. Mailing address: Department of Cardiology, The University of Texas-M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Phone: (713) 792-6242. Fax: (713) 745-1942. E-mail: etyeh{at}mdanderson.org.

Molecular and Cellular Biology, July 2004, p. 6021-6028, Vol. 24, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.13.6021-6028.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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