title: PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at the inhibitory site.
abstract: Contact inhibition has been largely elusive despite that a loss of contact inhibition is a critical event for cancer development and progression. Here, we report that PHLPP1 is a binding protein for Mst1 and it modulates the Hippo pathway by dephosphorylating Mst1 at the inhibitory Thr(387) of Mst1. Yap1 was localized predominantly in the nucleus but marginally in the cytoplasm in HeLa cells under sparse conditions, whereas the functional protein was more directed to sequestration in the cytoplasm under dense environments. Furthermore, loss of PHLPP1 resulted in a failure of the apoptotic control. It is interesting that down-regulated expression of PHLPP1 appears to mimic the loss of contact inhibition, a hallmark of cancer.
authors.affiliation: Targeted Gene Regulation Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Deajeon, South Korea.
authors.forename: Sujin
authors.initials: S
authors.lastname: Jung
authors.affiliation: Targeted Gene Regulation Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Deajeon, South Korea.
authors.forename: Jeong Gu
authors.initials: JG
authors.lastname: Kang
authors.affiliation: Targeted Gene Regulation Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Deajeon, South Korea; Department of Biomolecular Science, University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon, South Korea.
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Targeted Gene Regulation Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Deajeon, South Korea.
authors.forename: Kyoung Jin
authors.initials: KJ
authors.lastname: Song
authors.affiliation: Targeted Gene Regulation Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Deajeon, South Korea; Department of Biomolecular Science, University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon, South Korea.
authors.forename: Jeong-Heon
authors.initials: JH
authors.lastname: Ko
authors.affiliation: Targeted Gene Regulation Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Deajeon, South Korea; Department of Biomolecular Science, University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon, South Korea. Electronic address: omsys1@kribb.re.kr.
authors.forename: Yong-Sam
authors.initials: YS
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017209:Apoptosis; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003260:Contact Inhibition / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D000090683:Hippo Signaling Pathway; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D010749:Phosphoprotein Phosphatases; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C095566:STK4 protein, human; D000099317:Hippo Kinases; C400601:PHLPP1 protein, human
keywords: Contact inhibition; Hippo pathway; Mst1; PHLPP1