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Lipin1 regulates PPARγ transcriptional activity

Authors
 Hee Eun Kim  ;  Eunju Bae  ;  Deok-yoon Jeong  ;  Min-Ji Kim  ;  Won-Ji Jin  ;  Sahng-Wook Park  ;  Gil-Soo Han  ;  George M. Carman  ;  Eunjin Koh  ;  Kyung-Sup Kim 
Citation
 BIOCHEMICAL JOURNAL, Vol.453(1) : 49-60, 2013 
Journal Title
 BIOCHEMICAL JOURNAL 
ISSN
 0264-6021 
Issue Date
2013
MeSH
3T3-L1 Cells ; Adipocytes/cytology ; Animals ; Cell Differentiation/drug effects ; HEK293 Cells ; Humans ; Mice ; NIH 3T3 Cells ; Nuclear Proteins/physiology* ; PPAR alpha/metabolism ; PPAR gamma/genetics* ; PPAR gamma/metabolism ; Phosphatidate Phosphatase/physiology* ; Transcription, Genetic/drug effects
Keywords
co-activator ; co-repressor ; lipin1 ; peroxisomeproliferator-activated receptor (PPAR)
Abstract
PPARγ (peroxisome-proliferator-activated receptor γ) is a master transcription factor involved in adipogenesis through regulating adipocyte-specific gene expression. Recently, lipin1 was found to act as a key factor for adipocyte maturation and maintenance by modulating the C/EBPα (CCAAT/enhancer-binding protein α) and PPARγ network; however, the precise mechanism by which lipin1 affects the transcriptional activity of PPARγ is largely unknown. The results of the present study show that lipin1 activates PPARγ by releasing co-repressors, NCoR1 (nuclear receptor co-repressor 1) and SMRT (silencing mediator of retinoid and thyroid hormone receptor), from PPARγ in the absence of the ligand rosiglitazone. We also identified a novel lipin1 TAD (transcriptional activation domain), between residues 217 and 399, which is critical for the activation of PPARγ, but not PPARα. Furthermore, this TAD is unique to lipin1 since this region does not show any homology with the other lipin isoforms, lipin2 and lipin3. The activity of the lipin1 TAD is enhanced by p300 and SRC-1 (steroid receptor co-activator 1), but not by PCAF (p300/CBP-associated factor) and PGC-1α (PPAR co-activator 1α). The physical interaction between lipin1 and PPARγ occurs at the lipin1 C-terminal region from residues 825 to 926, and the VXXLL motif at residue 885 is critical for binding with and the activation of PPARγ. The action of lipin1 as a co-activator of PPARγ enhanced adipocyte differentiation; the TAD and VXXLL motif played critical roles, but the catalytic activity of lipin1 was not directly involved. Collectively, these data suggest that lipin1 functions as a key regulator of PPARγ activity through its ability to release co-repressors and recruit co-activators via a mechanism other than PPARα activation.
Full Text
http://www.biochemj.org/bj/453/0049/bj4530049.htm
DOI
10.1042/BJ20121598
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Koh, Eun Jin(고은진) ORCID logo https://orcid.org/0000-0001-8967-6266
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Kim, Hee Eun(김희은)
Park, Sahng Wook(박상욱) ORCID logo https://orcid.org/0000-0002-9594-7074
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87060
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