Negative Modulation of RXRα Transcriptional Activity by Small Ubiquitin-related Modifier (SUMO) Modification and Its Reversal by SUMO-specific Protease SUSP1*

Retinoid X receptor α (RXRα) belongs to a family of ligand-activated transcription factors that regulate many aspects of metazoan life. Here we demonstrate that RXRα is a target substrate of a small ubiquitin-related modifier (SUMO)-specific protease, SUSP1, which is capable of controlling the transcriptional activity of RXRα. RXRα was modified by SUMO-1 in vivo as well as in vitro, and the Lys-108 residue within the IKPP sequence of RXRα AF-1 domain was identified as the major SUMO-1 acceptor site. Prevention of SUMO modification by Lys-to-Arg mutation led to an increase not only in the transcriptional activity of RXRα but also in the activity of its heterodimeric complex with retinoic acid receptor-α or peroxisome proliferator-activated receptor-γ (PPARγ). SUSP1 co-localized with RXRα in the nucleus and removed SUMO-1 from RXRα but not from androgen receptor or PPARγ. Moreover, overexpression of SUSP1 caused an increase in the transcriptional activity of RXRα, whereas small hairpin RNA-mediated knockdown of endogenous SUSP1 led to a decrease in RXRα activity. These results suggest that SUSP1 plays an important role in the control of the transcriptional activity of RXRα and thus in the RXRα-mediated cellular processes.

• Publication year

  2006

• Venue

  Journal of Biological Chemistry

• Publication date

  2006-10-13

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.M604033200PMID 16912044
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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