Distinct functional modes of SUMOylation for retinoid X receptor alpha

Wai Ping Lee, Sarita Jena, E. Patricia Rodriguez, Sinead P. O'Donovan, Carl Wagner, Peter Jurutka, Paul D. Thompson

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The present study investigated human retinoid X receptor alpha (hRXRα) as a substrate for modification with small ubiquitin like modifier (SUMO) and how members of the protein inhibitor of activated STAT (PIAS) family may impact upon this process. In agreement with a previous study, we validate Ubc9 to facilitate SUMOylation of hRXRα at lysine 108 but note this modification to occur for all isoforms rather than specifically with SUMO1 and to preferentially occur with the unliganded form of hRXRα. SUMOylation of hRXRα is significantly enhanced through PIAS4-mediated activity with lysine 245 identified as a specific SUMO2 acceptor site modified in a PIAS4-dependent fashion. While individual mutations at lysine 108 or 245 modestly increase receptor activity, the combined loss of SUMOylation at both sites significantly potentiates the transcriptional responsiveness of hRXRα suggesting both sites may cooperate in a DNA element-dependent context. Our findings highlight combinatorial effects of SUMOylation may regulate RXRα-directed signalling in a gene-specific fashion.

Original languageEnglish (US)
Pages (from-to)195-200
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume464
Issue number1
DOIs
StatePublished - Jul 20 2015

Fingerprint

Retinoid X Receptor alpha
Sumoylation
Lysine
Protein Inhibitors of Activated STAT
Ubiquitin
Protein Isoforms
Genes
Mutation
DNA
Substrates

Keywords

  • PIAS
  • Retinoid X receptor
  • SUMO
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Distinct functional modes of SUMOylation for retinoid X receptor alpha. / Lee, Wai Ping; Jena, Sarita; Rodriguez, E. Patricia; O'Donovan, Sinead P.; Wagner, Carl; Jurutka, Peter; Thompson, Paul D.

In: Biochemical and Biophysical Research Communications, Vol. 464, No. 1, 20.07.2015, p. 195-200.

Research output: Contribution to journalArticle

Lee, Wai Ping ; Jena, Sarita ; Rodriguez, E. Patricia ; O'Donovan, Sinead P. ; Wagner, Carl ; Jurutka, Peter ; Thompson, Paul D. / Distinct functional modes of SUMOylation for retinoid X receptor alpha. In: Biochemical and Biophysical Research Communications. 2015 ; Vol. 464, No. 1. pp. 195-200.
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