Ubiquitin Ligase NEDD4 Regulates PPAR? Stability and Adipocyte Differentiation in 3T3-L1 Cells.

ABSTRACT: Peroxisome proliferator-activated receptor-? (PPAR?) is a ligand-activated nuclear receptor which controls lipid and glucose metabolism. It is also the master regulator of adipogenesis. In adipocytes, ligand-dependent PPAR? activation is associated with proteasomal degradation; therefore, regulation of PPAR? 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 PPAR? and is a bona fide E3 ligase for PPAR?. NEDD4 increases PPAR? stability through the inhibition of its proteasomal degradation. Knockdown of NEDD4 in 3T3-L1 adipocytes reduces PPAR? protein levels and suppresses adipocyte conversion. PPAR? correlates positively with NEDD4 in obese adipose tissue. Together, these findings support NEDD4 as a novel regulator of adipogenesis by modulating the stability of PPAR?.

SUBMITTER: Li JJ 

PROVIDER: S-EPMC5137149 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature