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

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dc.contributor.authorE Kim-
dc.contributor.authorJeong Gu Kang-
dc.contributor.authorM J Kang-
dc.contributor.authorJ H Park-
dc.contributor.authorY J Kim-
dc.contributor.authorT H Kweon-
dc.contributor.authorH W Lee-
dc.contributor.authorE H Jho-
dc.contributor.authorY H Lee-
dc.contributor.authorS I Kim-
dc.contributor.authorE C Yi-
dc.contributor.authorH W Park-
dc.contributor.authorW H Yang-
dc.contributor.authorJ W Cho-
dc.date.accessioned2020-09-24T03:39:49Z-
dc.date.available2020-09-24T03:39:49Z-
dc.date.issued2020-
dc.identifier.issn0027-8424-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/22724-
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.publisherNatl Acad Sciences-
dc.titleO-GlcNAcylation on LATS2 disrupts the Hippo pathway by inhibiting its activity-
dc.title.alternativeO-GlcNAcylation on LATS2 disrupts the Hippo pathway by inhibiting its activity-
dc.typeArticle-
dc.citation.titleProceedings of National Academy of Sciences of United States of America-
dc.citation.number25-
dc.citation.endPage14269-
dc.citation.startPage14259-
dc.citation.volume117-
dc.contributor.affiliatedAuthorJeong Gu Kang-
dc.contributor.alternativeName김은아-
dc.contributor.alternativeName강정구-
dc.contributor.alternativeName강민정-
dc.contributor.alternativeName박재형-
dc.contributor.alternativeName김연정-
dc.contributor.alternativeName권태현-
dc.contributor.alternativeName이한웅-
dc.contributor.alternativeName조억훈-
dc.contributor.alternativeName이용호-
dc.contributor.alternativeName김승일-
dc.contributor.alternativeName이유진-
dc.contributor.alternativeName박현우-
dc.contributor.alternativeName양원호-
dc.contributor.alternativeName조진원-
dc.identifier.bibliographicCitationProceedings of National Academy of Sciences of United States of America, vol. 117, no. 25, pp. 14259-14269-
dc.identifier.doi10.1073/pnas.1913469117-
dc.subject.keywordHippo pathway-
dc.subject.keywordLATS2-
dc.subject.keywordMOB1-
dc.subject.keywordO-GlcNAcylation-
dc.subject.keywordcancer-
dc.subject.localHippo pathway-
dc.subject.localLATS2-
dc.subject.localMOB1-
dc.subject.localO-GlcNAcylation-
dc.subject.localCancers-
dc.subject.localcancer-
dc.subject.localCancer-
dc.description.journalClassY-
Appears in Collections:
Synthetic Biology and Bioengineering Research Institute > Genome Editing Research Center > 1. Journal Articles
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