Toggle Main Menu Toggle Search

Open Access padlockePrints

Differential regulation of the androgen receptor by protein phosphatase regulatory subunits

Lookup NU author(s): James Grey, Dr Dominic Jones, Laura Wilson, Dr Sirintra Nakjang, Jake Clayton, Dr Richard Temperley, Dr Emma Clark, Dr Luke Gaughan, Professor Craig Robson

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© Grey et al. The Androgen Receptor (AR) is a key molecule in the development, maintenance and progression of prostate cancer (PC). However, the relationship between the AR and co-regulatory proteins that facilitate AR activity in castrate resistant settings remain understudied. Here we show that protein phosphatase 1 regulatory subunits, identified from a phosphatase RNAi screen, direct PP1 catalytic subunits to a varied yet significant response in AR function. As such, we have characterised the PP1ß holoenzyme, myosin phosphatase (MLCP), as a novel ligand independent regulator of the AR. Sustained MLCP activity through down-regulation of the MLCP inhibitory subunit, PPP1R14C, results in impaired AR nuclear translocation, protein stability and transcriptional activity in distinct models of PC progression, culminating in restoration of a non-malignant prostate genotype. Phenotypically, a marked reduction in cell proliferation and migration, characterised by G1 cell cycle arrest is observed, confirming PP1 holoenzyme disruption as a novel treatment approach in PC.


Publication metadata

Author(s): Grey J, Jones D, Wilson L, Nakjang S, Clayton J, Temperley R, Clark E, Gaughan L, Robson C

Publication type: Article

Publication status: Published

Journal: Oncotarget

Year: 2018

Volume: 9

Issue: 3

Pages: 3922-3935

Online publication date: 04/12/2017

Acceptance date: 09/11/2017

ISSN (electronic): 1949-2553

Publisher: Impact Journals LLC

URL: https://doi.org/10.18632/oncotarget.22883

DOI: 10.18632/oncotarget.22883


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share