E6AP Promotes Prostate Cancer by Reducing P27 Expression

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 May 7

PMID 28477016

Citations 16

Authors

Dinesh Raghu

Piotr Jan Paul

Twishi Gulati

Siddhartha Deb

Christine Khoo

Andrea Russo

Enzo Gallo

Giovanni Blandino

Ai-Leen Chan

Elena Takano

Shahneen K Sandhu

Stephen B Fox

Scott Williams

Sue Haupt

Cristina Gamell

Ygal Haupt

Affiliations

Soon will be listed here.

Abstract

Prostate 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.

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