Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/1413
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dc.contributor.authorDas, Sanjeev-
dc.contributor.authorDeshmukh, Ruhi S.-
dc.contributor.authorSharma, Shalakha-
dc.date.accessioned2022-09-05T12:13:13Z-
dc.date.available2022-09-05T12:13:13Z-
dc.date.issued2018-11-
dc.identifier.urihttp://hdl.handle.net/123456789/1413-
dc.description.abstractCyclin F is a substrate recognition subunit of Skp1-Cul1-F-box protein (SCF) E3 ubiquitin ligase complex. Although there have been reports describing the role of cyclin F in the genotoxic stress response, its function under conditions of altered metabolic homeostasis remain unexplored. Here we report that cyclin F is induced upon metabolic stress in a FOXO1-dependent manner. Under metabolic stress conditions, cyclin F mediated polyubiquitylation of RBPJ at Lys315, leading to its proteasomal degradation. RBPJ regulated the expression of IDH1, which is often mutated to an oncogenic form IDH1R132H in cancers. Thus, metabolic stress-induced cyclin F attenuated the oncogenic functions of IDH1R132H in an RBPJ-dependent manner. Studies in mouse tumor models indicated that abrogation of cyclin F expression facilitates IDH1R132H-mediated tumorigenesis and metastasis. In addition, increased IDH1R132H levels correlated with reduced cyclin F levels in increasing grades of glioma. These findings highlight a novel aspect of cyclin F functions in inhibiting tumorigenesis and provide mechanistic insights into regulation of IDH1R132H Significance: These findings reveal mechanistic insights into the key role of the cyclin F-RBPJ axis in response to metabolic stress in cancer cells. Cancer Res; 78(22); 6386-98. ©2018 AACR.en_US
dc.language.isoenen_US
dc.publisherAmerican Association for Cancer Researchen_US
dc.titleCyclin F-Dependent Degradation of RBPJ Inhibits IDH1R132H-Mediated Tumorigenesisen_US
dc.typeArticleen_US
dc.journalCancer Resen_US
dc.volumeno78en_US
dc.issueno22en_US
dc.pages6386-6398en_US
Appears in Collections:Molecular Oncology, Publications

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