Thrap3 docks on phosphoserine 273 of PPARγ and controls diabetic gene programming
作者： Jang Hyun Choi , Sun-Sil Choi , Eun Sun Kim , Mark P. Jedrychowski , Yong Ryoul Yang
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摘要: Phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ) at Ser273 by cyclin-dependent kinase 5 (CDK5) in adipose tissue stimulates insulin resistance, but the underlying molecular mechanisms are unclear. We show here that Thrap3 (thyroid hormone receptor-associated protein 3) can directly interact with PPARγ when it is phosphorylated Ser273, and this interaction controls diabetic gene programming mediated phosphorylation PPARγ. Knockdown restores most genes dysregulated CDK5 action on cultured adipocytes. Importantly, reduced expression fat antisense oligonucleotides (ASOs) regulates a specific set genes, including key adipokines adiponectin adipsin, effectively improves hyperglycemia resistance high-fat-fed mice without affecting body weight. These data indicate plays crucial role controlling may provide opportunities for development new therapeutics obesity type 2 diabetes.
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