Abstract
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) is a transcriptional coregulator that plays a major role in controlling metabolism and mitochondrial biogenesis. We showed that a diabetes-associated single nucleotide polymorphism (Gly482Ser, SNP rs8192678) results in decreased protein stability and half-life in liver and β-cell lines and human-induced pluripotent stem cells. We have evidence that degradation of the S482 variant is mediated by phosphorylation at this site (mass spectrometry) by three potential kinases (NEK2, MARK4 and S6KB2).
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