| First Author | Li JJ | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 38550 | PubMed ID | 27917940 |
| Mgi Jnum | J:380336 | Mgi Id | MGI:6222562 |
| Doi | 10.1038/srep38550 | Citation | Li JJ, et al. (2016) Ubiquitin Ligase NEDD4 Regulates PPARgamma Stability and Adipocyte Differentiation in 3T3-L1 Cells. Sci Rep 6:38550 |
| abstractText | Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a ligand-activated nuclear receptor which controls lipid and glucose metabolism. It is also the master regulator of adipogenesis. In adipocytes, ligand-dependent PPARgamma activation is associated with proteasomal degradation; therefore, regulation of PPARgamma degradation may modulate its transcriptional activity. Here, we show that neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4), an E3 ubiquitin ligase, interacts with the hinge and ligand binding domains of PPARgamma and is a bona fide E3 ligase for PPARgamma. NEDD4 increases PPARgamma stability through the inhibition of its proteasomal degradation. Knockdown of NEDD4 in 3T3-L1 adipocytes reduces PPARgamma protein levels and suppresses adipocyte conversion. PPARgamma correlates positively with NEDD4 in obese adipose tissue. Together, these findings support NEDD4 as a novel regulator of adipogenesis by modulating the stability of PPARgamma. |
