Mst1 is an interacting protein that mediates PHLPPs' induced apoptosis
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Publisher version
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2010-06-02Keywords
Animals*Apoptosis
Cell Movement
Cell Proliferation
Cells, Cultured
Extracellular Signal-Regulated MAP Kinases
Hepatocyte Growth Factor
Humans
Mice
Nuclear ProteinsPhosphoprotein PhosphatasesPhosphorylationProtein Kinase CProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSignal TransductionCell Biology
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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.Source
Mol Cell. 2010 May 28;38(4):512-23. Link to article on publisher's siteDOI
10.1016/j.molcel.2010.03.017Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49466PubMed ID
20513427Related Resources
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