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dc.contributor.authorRaghu, D
dc.contributor.authorPaul, PJ
dc.contributor.authorGulati, T
dc.contributor.authorDeb, S
dc.contributor.authorKhoo, C
dc.contributor.authorRusso, A
dc.contributor.authorGallo, E
dc.contributor.authorBlandino, G
dc.contributor.authorChan, A-L
dc.contributor.authorTakano, E
dc.contributor.authorSandhu, SK
dc.contributor.authorFox, SB
dc.contributor.authorWilliams, S
dc.contributor.authorHaupt, S
dc.contributor.authorGamell, C
dc.contributor.authorHaupt, Y
dc.date.accessioned2021-02-04T01:22:24Z
dc.date.available2021-02-04T01:22:24Z
dc.date.issued2017-06-27
dc.identifierpii: 17224
dc.identifier.citationRaghu, D., Paul, P. J., Gulati, T., Deb, S., Khoo, C., Russo, A., Gallo, E., Blandino, G., Chan, A. -L., Takano, E., Sandhu, S. K., Fox, S. B., Williams, S., Haupt, S., Gamell, C. & Haupt, Y. (2017). E6AP promotes prostate cancer by reducing p27 expression. ONCOTARGET, 8 (26), pp.42939-42948. https://doi.org/10.18632/oncotarget.17224.
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/11343/259340
dc.description.abstractProstate cancer (PC) is the most common cancer in men. Elevated levels of E3 ligase, E6-Associated Protein (E6AP) were previously linked to PC, consistent with increased protein expression in a subset of PC patients. In cancers, irregular E3 ligase activity drives proteasomal degradation of tumor suppressor proteins. Accordingly, E3 ligase inhibitors define a rational therapy to restore tumor suppression. The relevant tumor suppressors targeted by E6AP in PC are yet to be fully identified. In this study we show that p27, a key cell cycle regulator, is a target of E6AP in PC. Down regulation of E6AP increases p27 expression and enhances its nuclear accumulation in PC. We demonstrate that E6AP regulates p27 expression by inhibiting its transcription in an E2F1-dependent manner. Concomitant knockdown of E6AP and p27 partially restores PC cell growth, supporting the contribution of p27 to the overall effect of E6AP on prostate tumorigenesis. Overall, we unravelled the E6AP-p27 axis as a new promoter of PC, exposing an attractive target for therapy through the restoration of tumor suppression.
dc.languageEnglish
dc.publisherIMPACT JOURNALS LLC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleE6AP promotes prostate cancer by reducing p27 expression
dc.typeJournal Article
dc.identifier.doi10.18632/oncotarget.17224
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.affiliation.departmentClinical Pathology
melbourne.affiliation.departmentBio21
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.affiliation.facultyAffiliate
melbourne.source.titleOncotarget
melbourne.source.volume8
melbourne.source.issue26
melbourne.source.pages42939-42948
melbourne.identifier.nhmrc1063389
dc.rights.licenseCC BY
melbourne.elementsid1210136
melbourne.contributor.authorGulati, Twishi
melbourne.contributor.authorSandhu, Shahneen
melbourne.contributor.authorFox, Stephen
melbourne.contributor.authorWilliams, Scott
melbourne.contributor.authorGamell-Fulla, Cristina
melbourne.contributor.authorHaupt, Ygal
melbourne.contributor.authorRaghu, Dinesh
melbourne.contributor.authorPaul, Piotr Jan
melbourne.contributor.authorHaupt, Susan
dc.identifier.eissn1949-2553
melbourne.identifier.fundernameidCANCER COUNCIL VICTORIA, 1085154
melbourne.identifier.fundernameidNHMRC, 1063389
melbourne.accessrightsOpen Access


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