title: Ubiquitin Ligase NEDD4 Regulates PPARγ Stability and Adipocyte Differentiation in 3T3-L1 Cells.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee 38103, USA.
authors.forename: Jing Jing
authors.initials: JJ
authors.lastname: Li
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee 38103, USA.
authors.forename: Ruishan
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Pharmacology &Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Rati
authors.initials: R
authors.lastname: Lama
authors.affiliation: Department of Pharmacology &Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Xinjiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Ubiquitin Biology Laboratory, Pennington Biomedical Research Center, Louisiana State University Systems, Baton Rouge, LA 70808, USA.
authors.forename: Z Elizabeth
authors.initials: ZE
authors.lastname: Floyd
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee 38103, USA.|Department of Veterans Affairs Medical Center, Memphis, Tennessee 38104, USA.
authors.forename: Edwards A
authors.initials: EA
authors.lastname: Park
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee 38103, USA.
authors.forename: Francesca-Fang
authors.initials: FF
authors.lastname: Liao
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D050156:Adipogenesis; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002454:Cell Differentiation; D006224:Cricetinae; D003412:Cricetulus; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008239:Lysine / Q000378:metabolism; D051379:Mice; D000075702:Nedd4 Ubiquitin Protein Ligases / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D047495:PPAR gamma / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D055550:Protein Stability; D059748:Proteolysis; D054875:Ubiquitination
chemical_list: D008024:Ligands; D047495:PPAR gamma; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618459:Nedd4 protein, mouse; D008239:Lysine