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dc.contributor.authorQiao, Meng
dc.contributor.authorWang, Yaqi
dc.contributor.authorXu, Xiaoen
dc.contributor.authorLu, Jing
dc.contributor.authorDong, Yougli
dc.contributor.authorTao, Wufan
dc.contributor.authorStein, Janet L.
dc.contributor.authorStein, Gary S.
dc.contributor.authorIglehart, James D.
dc.contributor.authorShi, Qian
dc.contributor.authorPardee, Arthur B.
dc.date2022-08-11T08:10:56.000
dc.date.accessioned2022-08-23T17:25:42Z
dc.date.available2022-08-23T17:25:42Z
dc.date.issued2010-06-02
dc.date.submitted2011-01-11
dc.identifier.citationMol Cell. 2010 May 28;38(4):512-23. <a href="http://dx.doi.org/10.1016/j.molcel.2010.03.017">Link to article on publisher's site</a>
dc.identifier.issn1097-2765 (Linking)
dc.identifier.doi10.1016/j.molcel.2010.03.017
dc.identifier.pmid20513427
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49466
dc.description.abstractPHLPP1 and PHLPP2 phosphatases exert their tumor-suppressing functions by dephosphorylation and inactivation of Akt in several breast cancer and glioblastoma cells. However, Akt, or other known targets of PHLPPs that include PKC and ERK, may not fully elucidate the physiological role of the multifunctional phosphatases, especially their powerful apoptosis induction function. Here, we show that PHLPPs induce apoptosis in cancer cells independent of the known targets of PHLPPs. We identified Mst1 as a binding partner that interacts with PHLPPs both in vivo and in vitro. PHLPPs dephosphorylate Mst1 on the T387 inhibitory site, which activate Mst1 and its downstream effectors p38 and JNK to induce apoptosis. The same T387 site can be phosphorylated by Akt. Thus, PHLPP, Akt, and Mst1 constitute an autoinhibitory triangle that controls the fine balance of apoptosis and proliferation that is cell type and context dependent.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=20513427&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/j.molcel.2010.03.017
dc.subjectAnimals
dc.subject*Apoptosis
dc.subjectCell Movement
dc.subjectCell Proliferation
dc.subjectCells, Cultured
dc.subjectExtracellular Signal-Regulated MAP Kinases
dc.subjectHepatocyte Growth Factor
dc.subjectHumans
dc.subjectMice
dc.subjectNuclear Proteins
dc.subjectPhosphoprotein Phosphatases
dc.subjectPhosphorylation
dc.subjectProtein Kinase C
dc.subjectProto-Oncogene Proteins
dc.subjectProto-Oncogene Proteins c-akt
dc.subjectSignal Transduction
dc.subjectCell Biology
dc.titleMst1 is an interacting protein that mediates PHLPPs' induced apoptosis
dc.typeJournal Article
dc.source.journaltitleMolecular cell
dc.source.volume38
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/stein/12
dc.identifier.contextkey1724052
html.description.abstract<p>PHLPP1 and PHLPP2 phosphatases exert their tumor-suppressing functions by dephosphorylation and inactivation of Akt in several breast cancer and glioblastoma cells. However, Akt, or other known targets of PHLPPs that include PKC and ERK, may not fully elucidate the physiological role of the multifunctional phosphatases, especially their powerful apoptosis induction function. Here, we show that PHLPPs induce apoptosis in cancer cells independent of the known targets of PHLPPs. We identified Mst1 as a binding partner that interacts with PHLPPs both in vivo and in vitro. PHLPPs dephosphorylate Mst1 on the T387 inhibitory site, which activate Mst1 and its downstream effectors p38 and JNK to induce apoptosis. The same T387 site can be phosphorylated by Akt. Thus, PHLPP, Akt, and Mst1 constitute an autoinhibitory triangle that controls the fine balance of apoptosis and proliferation that is cell type and context dependent.</p>
dc.identifier.submissionpathstein/12
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages512-23


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