The story so far: post-translational regulation of peroxisome proliferator-activated receptors by ubiquitination and SUMOylation.
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 (PPARα, PPARβ/δ, and PPARγ) in addition to the retinoid X receptor and PPARγ coactivator-1α 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.
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7525, USA.
Kristine M
KM
Wadosky
Monte S
MS
Willis
D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006801:Humans; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D058207:Sumoylation / Q000502:physiology*; D054875:Ubiquitination / Q000502:physiology*
D047492:Peroxisome Proliferator-Activated Receptors