Poly (A) binding protein cytoplasmic 1 is a novel co-regulator of the androgen receptor

Eisermann, K and Dar, JA and Dong, J and Wang, D and Masoodi, KZ and Wang, Z (2015) Poly (A) binding protein cytoplasmic 1 is a novel co-regulator of the androgen receptor. PLoS ONE, 10 (7).

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Abstract

The androgen receptor (AR) is a member of the steroid receptor superfamily that regulates gene expression in a ligand-dependent manner. The NTD of the AR plays a key role in AR transactivation including androgen-independent activation of the AR in castration-resistant prostate cancer (CRPC) cells. We recently reported that amino acids (a.a.) 50-250 of the NTD are capable of modulating AR nucleocytoplasmic trafficking. To further explore the mechanism associated with a.a. 50-250, GFP pull-down assays were performed in C4-2 CRPC cells transfected with GFP tagged a.a. 50-250 of the AR. Mass spectrometry analysis of the pulled down proteins identified poly (A) binding protein cytoplasmic 1 (PABPC1) interaction with this region of the AR. In silicoanalysis of gene expression data revealed PABPC1 up-regulation in prostate cancer tissue specimens and this up-regulation correlates to increased disease recurrence. Co-immunoprecipitation assays confirmed the association of PABPC1 with a.a. 50-250 of the NTD of the AR. Knockdown of PABPC1 decreased nuclear AR protein levels and inhibited androgen activation of the AR target PSA in LNCaP and C4-2 cells. Additionally, knockdown of PABPC1 inhibited transactivation of the PSA promoter by NAR (AR lacking the LBD) and attenuated proliferation of AR-positive prostate cancer cells. These findings suggest that PABPC1 is a novel co-regulator of the AR and may be a potential target for blocking activation of the AR in CRPC.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Eisermann, K Dar, JA Dong, J Wang, D daw112@pitt.edu DAW112 Masoodi, KZ Wang, Z wangz2@pitt.edu WANGZ2
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Saleem, Mohammad UNSPECIFIED UNSPECIFIED UNSPECIFIED
Centers:	Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date:	15 July 2015
Date Type:	Publication
Access Restriction:	No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title:	PLoS ONE
Volume:	10
Number:	7
DOI or Unique Handle:	10.1371/journal.pone.0128495
Institution:	University of Pittsburgh
Schools and Programs:	School of Medicine > Pharmacology and Chemical Biology School of Medicine > Urology
Refereed:	Yes
Date Deposited:	23 Aug 2016 14:21
Last Modified:	30 Mar 2021 13:56
URI:	http://d-scholarship.pitt.edu/id/eprint/28420

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