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

Wadosky KM, Willis MS. The story so far: post-translational regulation of peroxisome proliferator-activated receptors by ubiquitination and SUMOylation. Am J Physiol Heart Circ Physiol 302: H515-H526, 2012. First published October 28, 2011; doi:10.1152/ajpheart.00703.2011.-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 (PPAR alpha, PPAR beta/delta, and PPAR gamma) in addition to the retinoid X receptor and PPAR gamma coactivator-1 alpha 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.