SENP1 enhances androgen receptor-dependent transcription through desumoylation of histone deacetylase 1.
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.
Cheng
Jinke
J
Department of Cardiology, The University of Texas-M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Wang
Dachun
D
Wang
Zhengxin
Z
Yeh
Edward T H
ET
D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000502:physiology*; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D034741:RNA, Small Interfering / Q000494:pharmacology; D011944:Receptors, Androgen / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear; D025842:SUMO-1 Protein / Q000378:metabolism; D014158:Transcription, Genetic; D014452:Ubiquitins / Q000378:metabolism
D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D025842:SUMO-1 Protein; D014452:Ubiquitins; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases