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Modulation of fatty acid synthase degradation by concerted action of p38 MAP kinase, E3 ligase COP1, and SH2-tyrosine phosphatase Shp2

dc.contributor.authorYu, Jianxiu
dc.contributor.authorDeng, Rong
dc.contributor.authorZhu, Helen H.
dc.contributor.authorZhang, Sharon S.
dc.contributor.authorZhu, Changhong
dc.contributor.authorMontminy, Marc
dc.contributor.authorDavis, Roger J.
dc.contributor.authorFeng, Gen-Sheng
dc.date2022-08-11T08:08:16.000
dc.date.accessioned2022-08-23T15:48:57Z
dc.date.available2022-08-23T15:48:57Z
dc.date.issued2013-02-08
dc.date.submitted2016-02-19
dc.identifier.citationJ Biol Chem. 2013 Feb 8;288(6):3823-30. doi: 10.1074/jbc.M112.397885. Epub 2012 Dec 26. <a href="http://dx.doi.org/10.1074/jbc.M112.397885">Link to article on publisher's site</a>
dc.identifier.issn0021-9258 (Linking)
dc.identifier.doi10.1074/jbc.M112.397885
dc.identifier.pmid23269672
dc.identifier.urihttp://hdl.handle.net/20.500.14038/28322
dc.description.abstractThe Src-homology 2 (SH2) domain-containing tyrosine phosphatase Shp2 has been known to regulate various signaling pathways triggered by receptor and cytoplasmic tyrosine kinases. Here we describe a novel function of Shp2 in control of lipid metabolism by mediating degradation of fatty acid synthase (FASN). p38-phosphorylated COP1 accumulates in the cytoplasm and subsequently binds FASN through Shp2 here as an adapter, leading to FASN-Shp2-COP1 complex formation and FASN degradation mediated by ubiquitination pathway. By fasting p38 is activated and stimulates FASN protein degradation in mice. Consistently, the FASN protein levels are dramatically elevated in mouse liver and pancreas in which Shp2/Ptpn11 is selectively deleted. Thus, this study identifies a new activity for Shp2 in lipid metabolism.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23269672&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567637/
dc.subject3T3 Cells
dc.subjectAnimals
dc.subjectFatty Acid Synthase, Type I
dc.subjectHeLa Cells
dc.subjectHumans
dc.subjectLipid Metabolism
dc.subjectLiver
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectNuclear Proteins
dc.subjectPancreas
dc.subjectProtein Tyrosine Phosphatase, Non-Receptor Type 11
dc.subject*Proteolysis
dc.subjectUbiquitin-Protein Ligases
dc.subjectp38 Mitogen-Activated Protein Kinases
dc.subjectBiochemistry
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectMolecular Biology
dc.titleModulation of fatty acid synthase degradation by concerted action of p38 MAP kinase, E3 ligase COP1, and SH2-tyrosine phosphatase Shp2
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume288
dc.source.issue6
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/davis/5
dc.identifier.contextkey8179678
html.description.abstract<p>The Src-homology 2 (SH2) domain-containing tyrosine phosphatase Shp2 has been known to regulate various signaling pathways triggered by receptor and cytoplasmic tyrosine kinases. Here we describe a novel function of Shp2 in control of lipid metabolism by mediating degradation of fatty acid synthase (FASN). p38-phosphorylated COP1 accumulates in the cytoplasm and subsequently binds FASN through Shp2 here as an adapter, leading to FASN-Shp2-COP1 complex formation and FASN degradation mediated by ubiquitination pathway. By fasting p38 is activated and stimulates FASN protein degradation in mice. Consistently, the FASN protein levels are dramatically elevated in mouse liver and pancreas in which Shp2/Ptpn11 is selectively deleted. Thus, this study identifies a new activity for Shp2 in lipid metabolism.</p>
dc.identifier.submissionpathdavis/5
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages3823-30


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