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

Peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-activated nuclear receptor which controls lipid and glucose metabolism. It is also the master regulator of adipogenesis. In adipocytes, ligand-dependent PPARγ activation is associated with proteasomal degradation; therefore, regulation of PPARγ 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 PPARγ and is a bona fide E3 ligase for PPARγ. NEDD4 increases PPARγ stability through the inhibition of its proteasomal degradation. Knockdown of NEDD4 in 3T3-L1 adipocytes reduces PPARγ protein levels and suppresses adipocyte conversion. PPARγ correlates positively with NEDD4 in obese adipose tissue. Together, these findings support NEDD4 as a novel regulator of adipogenesis by modulating the stability of PPARγ.
Mesh Terms:
3T3-L1 Cells, Adipocytes, Adipogenesis, Adipose Tissue, Animals, CHO Cells, Cell Differentiation, Cricetinae, Cricetulus, Gene Knockdown Techniques, HEK293 Cells, Humans, Ligands, Lysine, Mice, Nedd4 Ubiquitin Protein Ligases, Obesity, PPAR gamma, Protein Binding, Protein Domains, Protein Stability, Proteolysis, Ubiquitination
Sci Rep
Date: Dec. 05, 2015
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