Cited 34 times in
O-GlcNAcylation on LATS2 disrupts the Hippo pathway by inhibiting its activity
DC Field | Value | Language |
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dc.contributor.author | 김승일 | - |
dc.contributor.author | 이용호 | - |
dc.date.accessioned | 2020-12-01T16:53:35Z | - |
dc.date.available | 2020-12-01T16:53:35Z | - |
dc.date.issued | 2020-06 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/180032 | - |
dc.description.abstract | The 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.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | National Academy of Sciences | - |
dc.relation.isPartOf | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Adaptor Proteins, Signal Transducing / metabolism | - |
dc.subject.MESH | Apoptosis | - |
dc.subject.MESH | Cell Proliferation | - |
dc.subject.MESH | HEK293 Cells | - |
dc.subject.MESH | Homeostasis | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Phosphorylation | - |
dc.subject.MESH | Protein-Serine-Threonine Kinases / metabolism* | - |
dc.subject.MESH | Tumor Suppressor Proteins / metabolism* | - |
dc.title | O-GlcNAcylation on LATS2 disrupts the Hippo pathway by inhibiting its activity | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Surgery (외과학교실) | - |
dc.contributor.googleauthor | Eunah Kim | - |
dc.contributor.googleauthor | Jeong Gu Kang | - |
dc.contributor.googleauthor | Min Jueng Kang | - |
dc.contributor.googleauthor | Jae Hyung Park | - |
dc.contributor.googleauthor | Yeon Jung Kim | - |
dc.contributor.googleauthor | Tae Hyun Kweon | - |
dc.contributor.googleauthor | Han-Woong Lee | - |
dc.contributor.googleauthor | Eek-Hoon Jho | - |
dc.contributor.googleauthor | Yong-Ho Lee | - |
dc.contributor.googleauthor | Seung-Il Kim | - |
dc.contributor.googleauthor | Eugene C Yi | - |
dc.contributor.googleauthor | Hyun Woo Park | - |
dc.contributor.googleauthor | Won Ho Yang | - |
dc.contributor.googleauthor | Jin Won Cho | - |
dc.identifier.doi | 10.1073/pnas.1913469117 | - |
dc.contributor.localId | A00658 | - |
dc.contributor.localId | A02989 | - |
dc.relation.journalcode | J02550 | - |
dc.identifier.eissn | 1091-6490 | - |
dc.identifier.pmid | 32513743 | - |
dc.subject.keyword | Hippo pathway | - |
dc.subject.keyword | LATS2 | - |
dc.subject.keyword | MOB1 | - |
dc.subject.keyword | O-GlcNAcylation | - |
dc.subject.keyword | cancer | - |
dc.contributor.alternativeName | Kim, Seung Il | - |
dc.contributor.affiliatedAuthor | 김승일 | - |
dc.contributor.affiliatedAuthor | 이용호 | - |
dc.citation.volume | 117 | - |
dc.citation.number | 25 | - |
dc.citation.startPage | 14259 | - |
dc.citation.endPage | 14269 | - |
dc.identifier.bibliographicCitation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.117(25) : 14259-14269, 2020-06 | - |
dc.identifier.rimsid | 67212 | - |
dc.type.rims | ART | - |
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