Cargando…

p68/DdX5 Supports β-Catenin & RNAP II during Androgen Receptor Mediated Transcription in Prostate Cancer

The DEAD box RNA helicase p68 (Ddx5) is an important androgen receptor (AR) transcriptional co-activator in prostate cancer (PCa) and is over-expressed in late stage disease. β-Catenin is a multifunctional protein with important structural and signalling functions which is up-regulated in PCa and si...

Descripción completa

Detalles Bibliográficos
Autores principales: Clark, Emma L., Hadjimichael, Christiana, Temperley, Richard, Barnard, Amy, Fuller-Pace, Frances V., Robson, Craig N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547877/
https://www.ncbi.nlm.nih.gov/pubmed/23349811
http://dx.doi.org/10.1371/journal.pone.0054150
_version_ 1782256249289572352
author Clark, Emma L.
Hadjimichael, Christiana
Temperley, Richard
Barnard, Amy
Fuller-Pace, Frances V.
Robson, Craig N.
author_facet Clark, Emma L.
Hadjimichael, Christiana
Temperley, Richard
Barnard, Amy
Fuller-Pace, Frances V.
Robson, Craig N.
author_sort Clark, Emma L.
collection PubMed
description The DEAD box RNA helicase p68 (Ddx5) is an important androgen receptor (AR) transcriptional co-activator in prostate cancer (PCa) and is over-expressed in late stage disease. β-Catenin is a multifunctional protein with important structural and signalling functions which is up-regulated in PCa and similar to p68, interacts with the AR to co-activate expression of AR target genes. Importantly, p68 forms complexes with nuclear β-Catenin and promotes gene transcription in colon cancer indicating a functional interplay between these two proteins in cancer progression. In this study, we explore the relationship of p68 and β-Catenin in PCa to assess their potential co-operation in AR-dependent gene expression, which may be of importance in the development of castrate resistant prostate cancer (CRPCa). We use immunoprecipitation to demonstrate a novel interaction between p68 and β-Catenin in the nucleus of PCa cells, which is androgen dependent in LNCaP cells but androgen independent in a hormone refractory derivative of the same cell line (representative of the CRPCa disease type). Enhanced AR activity is seen in androgen-dependent luciferase reporter assays upon transient co-transfection of p68 and β-Catenin as an additive effect, and p68-depleted Chromatin-Immunoprecipitation (ChIP) showed a decrease in the recruitment of the AR and β-Catenin to androgen responsive promoter regions. In addition, we found p68 immunoprecipitated with the processive and non-processive form of RNA polymerase II (RNAP II) and show p68 recruited to elongating regions of the AR mediated PSA gene, suggesting a role for p68 in facilitating RNAP II transcription of AR mediated genes. These results suggest p68 is important in facilitating β-Catenin and AR transcriptional activity in PCa cells.
format Online
Article
Text
id pubmed-3547877
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-35478772013-01-24 p68/DdX5 Supports β-Catenin & RNAP II during Androgen Receptor Mediated Transcription in Prostate Cancer Clark, Emma L. Hadjimichael, Christiana Temperley, Richard Barnard, Amy Fuller-Pace, Frances V. Robson, Craig N. PLoS One Research Article The DEAD box RNA helicase p68 (Ddx5) is an important androgen receptor (AR) transcriptional co-activator in prostate cancer (PCa) and is over-expressed in late stage disease. β-Catenin is a multifunctional protein with important structural and signalling functions which is up-regulated in PCa and similar to p68, interacts with the AR to co-activate expression of AR target genes. Importantly, p68 forms complexes with nuclear β-Catenin and promotes gene transcription in colon cancer indicating a functional interplay between these two proteins in cancer progression. In this study, we explore the relationship of p68 and β-Catenin in PCa to assess their potential co-operation in AR-dependent gene expression, which may be of importance in the development of castrate resistant prostate cancer (CRPCa). We use immunoprecipitation to demonstrate a novel interaction between p68 and β-Catenin in the nucleus of PCa cells, which is androgen dependent in LNCaP cells but androgen independent in a hormone refractory derivative of the same cell line (representative of the CRPCa disease type). Enhanced AR activity is seen in androgen-dependent luciferase reporter assays upon transient co-transfection of p68 and β-Catenin as an additive effect, and p68-depleted Chromatin-Immunoprecipitation (ChIP) showed a decrease in the recruitment of the AR and β-Catenin to androgen responsive promoter regions. In addition, we found p68 immunoprecipitated with the processive and non-processive form of RNA polymerase II (RNAP II) and show p68 recruited to elongating regions of the AR mediated PSA gene, suggesting a role for p68 in facilitating RNAP II transcription of AR mediated genes. These results suggest p68 is important in facilitating β-Catenin and AR transcriptional activity in PCa cells. Public Library of Science 2013-01-17 /pmc/articles/PMC3547877/ /pubmed/23349811 http://dx.doi.org/10.1371/journal.pone.0054150 Text en © 2013 Clark et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Clark, Emma L.
Hadjimichael, Christiana
Temperley, Richard
Barnard, Amy
Fuller-Pace, Frances V.
Robson, Craig N.
p68/DdX5 Supports β-Catenin & RNAP II during Androgen Receptor Mediated Transcription in Prostate Cancer
title p68/DdX5 Supports β-Catenin & RNAP II during Androgen Receptor Mediated Transcription in Prostate Cancer
title_full p68/DdX5 Supports β-Catenin & RNAP II during Androgen Receptor Mediated Transcription in Prostate Cancer
title_fullStr p68/DdX5 Supports β-Catenin & RNAP II during Androgen Receptor Mediated Transcription in Prostate Cancer
title_full_unstemmed p68/DdX5 Supports β-Catenin & RNAP II during Androgen Receptor Mediated Transcription in Prostate Cancer
title_short p68/DdX5 Supports β-Catenin & RNAP II during Androgen Receptor Mediated Transcription in Prostate Cancer
title_sort p68/ddx5 supports β-catenin & rnap ii during androgen receptor mediated transcription in prostate cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547877/
https://www.ncbi.nlm.nih.gov/pubmed/23349811
http://dx.doi.org/10.1371/journal.pone.0054150
work_keys_str_mv AT clarkemmal p68ddx5supportsbcateninrnapiiduringandrogenreceptormediatedtranscriptioninprostatecancer
AT hadjimichaelchristiana p68ddx5supportsbcateninrnapiiduringandrogenreceptormediatedtranscriptioninprostatecancer
AT temperleyrichard p68ddx5supportsbcateninrnapiiduringandrogenreceptormediatedtranscriptioninprostatecancer
AT barnardamy p68ddx5supportsbcateninrnapiiduringandrogenreceptormediatedtranscriptioninprostatecancer
AT fullerpacefrancesv p68ddx5supportsbcateninrnapiiduringandrogenreceptormediatedtranscriptioninprostatecancer
AT robsoncraign p68ddx5supportsbcateninrnapiiduringandrogenreceptormediatedtranscriptioninprostatecancer