Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/1412
Full metadata record
DC FieldValueLanguage
dc.contributor.authorDas, Sanjeev-
dc.contributor.authorKohli, Saishruti-
dc.contributor.authorBhardwaj, Abhishek-
dc.contributor.authorKumari, Richa-
dc.date.accessioned2022-09-05T12:03:40Z-
dc.date.available2022-09-05T12:03:40Z-
dc.date.issued2018-02-
dc.identifier.urihttp://hdl.handle.net/123456789/1412-
dc.description.abstractUBE3A is an E3 ubiquitin ligase well known for its role in the proteasomal degradation of p53 in human papillomavirus (HPV)-associated cancers. Here we report that UBE3A ubiquitylates and triggers degradation of the tumor-suppressive sirtuin SIRT6 in hepatocellular carcinoma. UBE3A ubiquitylated the highly conserved Lys160 residue on SIRT6. FOXO1-mediated transcriptional repression of UBE3A was sufficient to stabilize SIRT6 and to epigenetically repress ANXA2, a key mediator of UBE3A oncogenic function. Thus, UBE3A-mediated SIRT6 degradation promoted the proliferative capacity, migration potential, and invasiveness of cells. In mouse models of hepatocellular carcinoma, SIRT6 downregulation and consequent induction of ANXA2 were critical for UBE3A-mediated tumorigenesis. Furthermore, in clinical specimens, increased UBE3A levels correlated with reduced SIRT6 levels and elevated ANXA2 levels in increasing tumor grades. Overall, our findings show how the tumor suppressor SIRT6 is regulated in hepatocellular carcinoma and establish the mechanism underlying UBE3A-mediated tumorigenesis in this disease.Significance: These findings provide mechanistic insights into regulation of the tumor suppressive sirtuin SIRT6 and its implications for the development of hepatocellular carcinoma. Cancer Res; 78(3); 645-58. ©2017 AACRen_US
dc.language.isoenen_US
dc.publisherAmerican Association for Cancer Researchen_US
dc.titleSIRT6 Is a Target of Regulation by UBE3A That Contributes to Liver Tumorigenesis in an ANXA2-Dependent Manneren_US
dc.typeArticleen_US
dc.journalCancer Resen_US
dc.volumeno78en_US
dc.issueno3en_US
dc.pages645-658en_US
Appears in Collections:Molecular Oncology, Publications

Files in This Item:
File Description SizeFormat 
645.pdf4.02 MBAdobe PDFView/Open    Request a copy


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.