The story so far: Post-translational regulation of peroxisome proliferator-activated receptors by ubiquitination and sumoylation

Kristine M. Wadosky, Monte S. Willis

Research output: Contribution to journalReview article

50 Scopus citations

Abstract

Many studies have implicated the peroxisome proliferator-activated receptor (PPAR) family of nuclear receptor transcription factors in regulating cardiac substrate metabolism and ATP generation. Recently, evidence from a variety of cell culture and organ systems has implicated ubiquitin and small ubiquitin-like modifier (SUMO) conjugation as post-translational modifications that regulate the activity of PPAR transcription factors and their coreceptors/coactivators. Here we introduce the ubiquitin and SUMO conjugation systems and extensively review how they have been shown to regulate all three PPAR isoforms (PPARa, PPAR(3/8, and PPAR7) in addition to the retinoid X receptor and PPAR7 coactivator-1a subunits of the larger PPAR transcription factor complex. We then present how the specific ubiquitin (E3) ligases have been implicated and review emerging evidence that post-translational modifications of PPARs with ubiquitin and/or SUMO may play a role in cardiac disease. Because PPAR activity is perturbed in a variety of forms of heart disease and specific proteins regulate this process (E3 ligases), this may be a fruitful area of investigation with respect to finding new therapeutic targets.

Original languageEnglish (US)
Pages (from-to)H515-H526
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume302
Issue number3
DOIs
StatePublished - Feb 2012

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Keywords

  • Phosphorylation
  • Retinoid x receptor
  • Small ubiquitin-like modifier
  • Ubiquitin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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