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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.

Pubmed ID: 15199155

Authors

  • Cheng J
  • Wang D
  • Wang Z
  • Yeh ET

Journal

Molecular and cellular biology

Publication Data

July 16, 2004

Associated Grants

  • Agency: NCI NIH HHS, Id: R01 CA 80089
  • Agency: NIDDK NIH HHS, Id: R01 DK065156

Mesh Terms

  • Cell Line, Tumor
  • Endopeptidases
  • Gene Expression Regulation
  • Histone Deacetylase 1
  • Histone Deacetylases
  • Humans
  • RNA, Small Interfering
  • Receptors, Androgen
  • Receptors, Cytoplasmic and Nuclear
  • SUMO-1 Protein
  • Transcription, Genetic
  • Ubiquitins