PIASy-Mediated Sumoylation of SREBP1c Regulates Hepatic Lipid Metabolism upon Fasting Signaling

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dc.contributor.authorLee, Gha Youngko
dc.contributor.authorJang, Hagoonko
dc.contributor.authorLee, Jae Hoko
dc.contributor.authorHuh, Jin Youngko
dc.contributor.authorChoi, Sekyuko
dc.contributor.authorChung, Jongkyeongko
dc.contributor.authorKim, Jae Bumko
dc.date.accessioned2014-08-29T01:38:24Z-
dc.date.available2014-08-29T01:38:24Z-
dc.date.created2014-04-14-
dc.date.created2014-04-14-
dc.date.issued2014-03-
dc.identifier.citationMOLECULAR AND CELLULAR BIOLOGY, v.34, no.6, pp.926 - 938-
dc.identifier.issn0270-7306-
dc.identifier.urihttp://hdl.handle.net/10203/188835-
dc.description.abstractSREBP1c is a key transcription factor that regulates de novo lipogenesis during anabolic periods. However, the molecular mechanisms involved in the suppression of SREBP1c under nutritional deprivation are largely unknown. In this study, we demonstrate that the small ubiquitin-related modifier (SUMO) E3 ligase, a protein inhibitor of activated STAT Y (PIASy), sumoylates SREBP1c at Lys98, leading to suppression of the hepatic lipogenic program upon fasting-induced signals. In primary hepatocytes, ablation of PIASy stimulated intracellular lipid accumulation through the induction of SREBP1c and its target genes. Given that protein kinase A (PKA) plays important roles in catabolic responses, activated PKA enhances the sumoylation of SREBP1c and potentiates the interaction between SREBP1c and PIASy. Notably, overexpression of PIASy in obese db/db mice ameliorated hepatic steatosis, while suppression of PIASy in lean (wild-type) mice stimulated hepatic lipogenesis with increased expression of SREBP1c target genes. Furthermore, PKA-mediated SREBP1c phosphorylation augmented SREBP1c sumoylation, subsequently leading to degradation of SREBP1c via ubiquitination. Together, these data suggest that PKA-induced SREBP1c sumoylation by PIASy is a key regulatory mechanism to turn off hepatic lipogenesis during nutritional deprivation.-
dc.languageEnglish-
dc.publisherAMER SOC MICROBIOLOGY-
dc.subjectELEMENT-BINDING PROTEINS-
dc.subjectBOUND TRANSCRIPTION FACTOR-
dc.subjectGENE-EXPRESSION-
dc.subjectSUMO-1 MODIFICATION-
dc.subjectPROTEASOME PATHWAY-
dc.subjectRAT HEPATOCYTES-
dc.subjectTARGET GENES-
dc.subjectINSULIN-
dc.subjectPHOSPHORYLATION-
dc.subjectCHOLESTEROL-
dc.titlePIASy-Mediated Sumoylation of SREBP1c Regulates Hepatic Lipid Metabolism upon Fasting Signaling-
dc.typeArticle-
dc.identifier.wosid000331995800002-
dc.identifier.scopusid2-s2.0-84894241362-
dc.type.rimsART-
dc.citation.volume34-
dc.citation.issue6-
dc.citation.beginningpage926-
dc.citation.endingpage938-
dc.citation.publicationnameMOLECULAR AND CELLULAR BIOLOGY-
dc.identifier.doi10.1128/MCB.01166-13-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.contributor.localauthorChoi, Sekyu-
dc.contributor.nonIdAuthorLee, Gha Young-
dc.contributor.nonIdAuthorJang, Hagoon-
dc.contributor.nonIdAuthorLee, Jae Ho-
dc.contributor.nonIdAuthorHuh, Jin Young-
dc.contributor.nonIdAuthorChung, Jongkyeong-
dc.contributor.nonIdAuthorKim, Jae Bum-
dc.type.journalArticleArticle-
dc.subject.keywordPlusELEMENT-BINDING PROTEINS-
dc.subject.keywordPlusBOUND TRANSCRIPTION FACTOR-
dc.subject.keywordPlusGENE-EXPRESSION-
dc.subject.keywordPlusSUMO-1 MODIFICATION-
dc.subject.keywordPlusPROTEASOME PATHWAY-
dc.subject.keywordPlusRAT HEPATOCYTES-
dc.subject.keywordPlusTARGET GENES-
dc.subject.keywordPlusINSULIN-
dc.subject.keywordPlusPHOSPHORYLATION-
dc.subject.keywordPlusCHOLESTEROL-
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