| First Author | Kim JH | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 40023 | PubMed ID | 28059128 |
| Mgi Jnum | J:316583 | Mgi Id | MGI:6831982 |
| Doi | 10.1038/srep40023 | Citation | Kim JH, et al. (2017) C-terminus of HSC70-Interacting Protein (CHIP) Inhibits Adipocyte Differentiation via Ubiquitin- and Proteasome-Mediated Degradation of PPARgamma. Sci Rep 7:40023 |
| abstractText | PPARgamma (Peroxisome proliferator-activated receptor gamma) is a nuclear receptor involved in lipid homeostasis and related metabolic diseases. Acting as a transcription factor, PPARgamma is a master regulator for adipocyte differentiation. Here, we reveal that CHIP (C-terminus of HSC70-interacting protein) suppresses adipocyte differentiation by functioning as an E3 ligase of PPARgamma. CHIP directly binds to and induces ubiquitylation of the PPARgamma protein, leading to proteasome-dependent degradation. Stable overexpression or knockdown of CHIP inhibited or promoted adipogenesis, respectively, in 3T3-L1 cells. On the other hand, a CHIP mutant defective in E3 ligase could neither regulate PPARgamma protein levels nor suppress adipogenesis, indicating the importance of CHIP-mediated ubiquitylation of PPARgamma in adipocyte differentiation. Lastly, a CHIP null embryo fibroblast exhibited augmented adipocyte differentiation with increases in PPARgamma and its target protein levels. In conclusion, CHIP acts as an E3 ligase of PPARgamma, suppressing PPARgamma-mediated adipogenesis. |
