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CRL4A-FBXW5-mediated degradation of DLC1 Rho GTPase-activating protein tumor suppressor promotes non-small cell lung cancer cell growth
DC Field | Value | Language |
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dc.contributor.author | Kim, Tai Young | - |
dc.contributor.author | Jackson, Sarah | - |
dc.contributor.author | Xiong, Yue | - |
dc.contributor.author | Whitsett, Timothy G. | - |
dc.contributor.author | Lobello, Janine R. | - |
dc.contributor.author | Weiss, Glen J. | - |
dc.contributor.author | Le Tran, Nhan | - |
dc.contributor.author | Bang, Yung-Jue | - |
dc.contributor.author | Der, Channing J. | - |
dc.date.accessioned | 2021-01-31T11:56:27Z | - |
dc.date.available | 2021-01-31T11:56:27Z | - |
dc.date.created | 2020-12-16 | - |
dc.date.created | 2020-12-16 | - |
dc.date.issued | 2013-10 | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, Vol.110 No.42, pp.16868-16873 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.other | 119245 | - |
dc.identifier.uri | https://hdl.handle.net/10371/173152 | - |
dc.description.abstract | DLC1 encodes a RhoA GTPase-activating protein and tumor suppressor lost in cancer by genomic deletion or epigenetic silencing and loss of DLC1 gene transcription. We unexpectedly identified non-small cell lung cancer (NSCLC) cell lines and tumor tissue that expressed DLC1 mRNA yet lacked DLC1 protein expression. We determined that DLC1 was ubiquitinated and degraded by cullin 4A-RING ubiquitin ligase (CRL4A) complex interaction with DDB1 and the FBXW5 substrate receptor. siRNA-mediated suppression of cullin 4A, DDB1, or FBXW5 expression restored DLC1 protein expression in NSCLC cell lines. FBXW5 suppression-induced DLC1 reexpression was associated with a reduction in the levels of activated RhoA-GTP and in RhoA effector signaling. Finally, FBXW5 suppression caused a DLC1-dependent decrease in NSCLC anchorage-dependent and -independent proliferation. In summary, we identify a posttranslational mechanism for loss of DLC1 and a linkage between CRL4-AFBXW5-associated oncogenesis and regulation of RhoA signaling. | - |
dc.language | 영어 | - |
dc.publisher | National Academy of Sciences | - |
dc.title | CRL4A-FBXW5-mediated degradation of DLC1 Rho GTPase-activating protein tumor suppressor promotes non-small cell lung cancer cell growth | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 방영주 | - |
dc.identifier.doi | 10.1073/pnas.1306358110 | - |
dc.citation.journaltitle | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.identifier.wosid | 000325634200044 | - |
dc.identifier.scopusid | 2-s2.0-84885706043 | - |
dc.citation.endpage | 16873 | - |
dc.citation.number | 42 | - |
dc.citation.startpage | 16868 | - |
dc.citation.volume | 110 | - |
dc.identifier.sci | 000325634200044 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Bang, Yung-Jue | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | HEPATOCELLULAR-CARCINOMA | - |
dc.subject.keywordPlus | ABERRANT METHYLATION | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | TARGETS | - |
dc.subject.keywordPlus | LIGASE | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | MIGRATION | - |
dc.subject.keywordPlus | INVASION | - |
dc.subject.keywordPlus | METASTASIS | - |
dc.subject.keywordPlus | FAMILY | - |
dc.subject.keywordAuthor | Rho-selective GTPase-activating protein | - |
dc.subject.keywordAuthor | Rho GTPase-activating protein 7 | - |
dc.subject.keywordAuthor | STARD12 | - |
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