| First Author | Choi JH | Year | 2014 |
| Journal | Genes Dev | Volume | 28 |
| Issue | 21 | Pages | 2361-9 |
| PubMed ID | 25316675 | Mgi Jnum | J:217435 |
| Mgi Id | MGI:5613882 | Doi | 10.1101/gad.249367.114 |
| Citation | Choi JH, et al. (2014) Thrap3 docks on phosphoserine 273 of PPARgamma and controls diabetic gene programming. Genes Dev 28(21):2361-9 |
| abstractText | Phosphorylation of peroxisome proliferator-activated receptor gamma (PPARgamma) 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 PPARgamma when it is phosphorylated at Ser273, and this interaction controls the diabetic gene programming mediated by the phosphorylation of PPARgamma. Knockdown of Thrap3 restores most of the genes dysregulated by CDK5 action on PPARgamma in cultured adipocytes. Importantly, reduced expression of Thrap3 in fat tissue by antisense oligonucleotides (ASOs) regulates a specific set of genes, including the key adipokines adiponectin and adipsin, and effectively improves hyperglycemia and insulin resistance in high-fat-fed mice without affecting body weight. These data indicate that Thrap3 plays a crucial role in controlling diabetic gene programming and may provide opportunities for the development of new therapeutics for obesity and type 2 diabetes. |
