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O-GlcNAcylation on LATS2 disrupts the Hippo pathway by inhibiting its activity

DC FieldValueLanguage
dc.contributor.author김승일-
dc.contributor.author이용호-
dc.date.accessioned2020-12-01T16:53:35Z-
dc.date.available2020-12-01T16:53:35Z-
dc.date.issued2020-06-
dc.identifier.issn0027-8424-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/180032-
dc.description.abstractThe Hippo pathway controls organ size and tissue homeostasis by regulating cell proliferation and apoptosis. The LATS-mediated negative feedback loop prevents excessive activation of the effectors YAP/TAZ, maintaining homeostasis of the Hippo pathway. YAP and TAZ are hyperactivated in various cancer cells which lead to tumor growth. Aberrantly increased O-GlcNAcylation has recently emerged as a cause of hyperactivation of YAP in cancer cells. However, the mechanism, which induces hyperactivation of TAZ and blocks LATS-mediated negative feedback, remains to be elucidated in cancer cells. This study found that in breast cancer cells, abnormally increased O-GlcNAcylation hyperactivates YAP/TAZ and inhibits LATS2, a direct negative regulator of YAP/TAZ. LATS2 is one of the newly identified O-GlcNAcylated components in the MST-LATS kinase cascade. Here, we found that O-GlcNAcylation at LATS2 Thr436 interrupted its interaction with the MOB1 adaptor protein, which connects MST to LATS2, leading to activation of YAP/TAZ by suppressing LATS2 kinase activity. LATS2 is a core component in the LATS-mediated negative feedback loop. Thus, this study suggests that LATS2 O-GlcNAcylation is deeply involved in tumor growth by playing a critical role in dysregulation of the Hippo pathway in cancer cells.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherNational Academy of Sciences-
dc.relation.isPartOfPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAdaptor Proteins, Signal Transducing / metabolism-
dc.subject.MESHApoptosis-
dc.subject.MESHCell Proliferation-
dc.subject.MESHHEK293 Cells-
dc.subject.MESHHomeostasis-
dc.subject.MESHHumans-
dc.subject.MESHPhosphorylation-
dc.subject.MESHProtein-Serine-Threonine Kinases / metabolism*-
dc.subject.MESHTumor Suppressor Proteins / metabolism*-
dc.titleO-GlcNAcylation on LATS2 disrupts the Hippo pathway by inhibiting its activity-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Surgery (외과학교실)-
dc.contributor.googleauthorEunah Kim-
dc.contributor.googleauthorJeong Gu Kang-
dc.contributor.googleauthorMin Jueng Kang-
dc.contributor.googleauthorJae Hyung Park-
dc.contributor.googleauthorYeon Jung Kim-
dc.contributor.googleauthorTae Hyun Kweon-
dc.contributor.googleauthorHan-Woong Lee-
dc.contributor.googleauthorEek-Hoon Jho-
dc.contributor.googleauthorYong-Ho Lee-
dc.contributor.googleauthorSeung-Il Kim-
dc.contributor.googleauthorEugene C Yi-
dc.contributor.googleauthorHyun Woo Park-
dc.contributor.googleauthorWon Ho Yang-
dc.contributor.googleauthorJin Won Cho-
dc.identifier.doi10.1073/pnas.1913469117-
dc.contributor.localIdA00658-
dc.contributor.localIdA02989-
dc.contributor.localIdA02989-
dc.relation.journalcodeJ02550-
dc.identifier.eissn1091-6490-
dc.identifier.pmid32513743-
dc.subject.keywordHippo pathway-
dc.subject.keywordLATS2-
dc.subject.keywordMOB1-
dc.subject.keywordO-GlcNAcylation-
dc.subject.keywordcancer-
dc.contributor.alternativeNameKim, Seung Il-
dc.contributor.affiliatedAuthor김승일-
dc.contributor.affiliatedAuthor이용호-
dc.contributor.affiliatedAuthor이용호-
dc.citation.volume117-
dc.citation.number25-
dc.citation.startPage14259-
dc.citation.endPage14269-
dc.identifier.bibliographicCitationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.117(25) : 14259-14269, 2020-06-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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