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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...

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Autores principales: Li, Jing Jing, Wang, Ruishan, Lama, Rati, Wang, Xinjiang, Floyd, Z. Elizabeth, Park, Edwards A., Liao, Francesca-Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137149/
https://www.ncbi.nlm.nih.gov/pubmed/27917940
http://dx.doi.org/10.1038/srep38550
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author Li, Jing Jing
Wang, Ruishan
Lama, Rati
Wang, Xinjiang
Floyd, Z. Elizabeth
Park, Edwards A.
Liao, Francesca-Fang
author_facet Li, Jing Jing
Wang, Ruishan
Lama, Rati
Wang, Xinjiang
Floyd, Z. Elizabeth
Park, Edwards A.
Liao, Francesca-Fang
author_sort Li, Jing Jing
collection PubMed
description 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.
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spelling pubmed-51371492017-01-27 Ubiquitin Ligase NEDD4 Regulates PPARγ Stability and Adipocyte Differentiation in 3T3-L1 Cells Li, Jing Jing Wang, Ruishan Lama, Rati Wang, Xinjiang Floyd, Z. Elizabeth Park, Edwards A. Liao, Francesca-Fang Sci Rep Article 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. Nature Publishing Group 2016-12-05 /pmc/articles/PMC5137149/ /pubmed/27917940 http://dx.doi.org/10.1038/srep38550 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Li, Jing Jing
Wang, Ruishan
Lama, Rati
Wang, Xinjiang
Floyd, Z. Elizabeth
Park, Edwards A.
Liao, Francesca-Fang
Ubiquitin Ligase NEDD4 Regulates PPARγ Stability and Adipocyte Differentiation in 3T3-L1 Cells
title Ubiquitin Ligase NEDD4 Regulates PPARγ Stability and Adipocyte Differentiation in 3T3-L1 Cells
title_full Ubiquitin Ligase NEDD4 Regulates PPARγ Stability and Adipocyte Differentiation in 3T3-L1 Cells
title_fullStr Ubiquitin Ligase NEDD4 Regulates PPARγ Stability and Adipocyte Differentiation in 3T3-L1 Cells
title_full_unstemmed Ubiquitin Ligase NEDD4 Regulates PPARγ Stability and Adipocyte Differentiation in 3T3-L1 Cells
title_short Ubiquitin Ligase NEDD4 Regulates PPARγ Stability and Adipocyte Differentiation in 3T3-L1 Cells
title_sort ubiquitin ligase nedd4 regulates pparγ stability and adipocyte differentiation in 3t3-l1 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137149/
https://www.ncbi.nlm.nih.gov/pubmed/27917940
http://dx.doi.org/10.1038/srep38550
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