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Seminars

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[Seminar Notification] :Jang Hyun Choi, Ph.D. (12.13.2018)
2018-12-07

1. Title::Post-translational modification of PPAR and energy metabolism
2. Speaker: Jang Hyun Choi, Ph.D.
3. Affiliation:Department of Biological Sciences, UNIST
4. Date: 2018. 12.13. (Thu) 16:00
5. Place: SIMS Main Building, Auditorium 109(1F)
6. Abstract:

Phosphorylation of 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 at Ser273, and this interaction controls the diabetic gene programing mediated by the phosphorylation of PPARγ. Importantly, reduced expression of Thrap3 in fat tissue by antisense oligonucleotides (ASO) 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 programing, and may provide opportunities for the development of new therapeutics for obesity and type 2 diabetes. In addition, I will discuss the physiological roles of Thrap3 specifically in liver in detail.

 

PPARis a ligand-dependent transcription factor which regulates adipocyte differentiation and glucose homeostasis. Its transcriptional activity is regulated by not only ligands but also post-translational modifications (PTMs). Here, we demonstrate a novel E3 ligase of PPAR, TRIM25 directly induces ubiquitination of PPARfollowed by proteasome-dependent degradation. During the adipocyte differentiation, both mRNA and protein expression of TRIM25 significantly decreased and negatively correlated with the expression of PPAR. Stable expression of TRIM25 reduces PPARprotein levels, but not mRNA expression, and suppressed adipocyte differentiation in 3T3-L1 cells. In contrast, specific knock-down of TRIM25 increases PPARprotein levels and stimulated adipocyte differentiation. Furthermore, TRIM25 knock-out mouse embryonic fibroblast (MEFs) shows an increased ability for adipocyte differentiation compared with wild-type MEFs. Taken together, these data indicate that TRIM25 is a novel E3 ubiquitin ligase of PPAR, and depict TRIM25 as a novel target for PPAR-involved metabolic diseases.