Prostate cancer (PCa) growth requires tethering of the androgen receptor (AR) to chromatin by the ETS domain transcription factor ELK1 to coactivate critical cell proliferation genes. Disruption of the ELK1–AR complex is a validated potential means of therapeutic intervention in PCa. AR associates with ELK1 by coopting its two ERK docking sites, through the amino-terminal domain (A/B domain) of AR. Using a mammalian two-hybrid assay, we have now functionally mapped amino acids within the peptide segments 358–457 and 514–557 in the A/B domain as required for association with ELK1. The mapping data were validated by GST (glutathione S-transferase)-pulldown and BRET (bioluminescence resonance energy transfer) assays. Comparison of the relative contributions of the interacting motifs/segments in ELK1 and AR to coactivation of ELK1 by AR suggested a parallel mode of binding of AR and ELK1 polypeptides. Growth of PCa cells was partially inhibited by deletion of the upstream segment in AR and nearly fully inhibited by deletion of the downstream segment. Our studies have identified two peptide segments in AR that mediate the functional association of AR with its two docking sites in ELK1. Identification of the ELK1 recognition sites in AR should enable further structural studies of the ELK1–AR interaction and rational design of small molecule drugs to disrupt this interaction.
Skip Nav Destination
Article navigation
July 2022
-
Cover Image
Cover Image
The cover image shows the double hexameric ring structures of Mycobacterium tuberculosis EccCb1 in apo and EsxAB+ATP+Mg2+ bound forms. The binding affinity EsxAB substrate to EccCb1 is enhanced ~2-fold in presence of ATP and Mg2+, which indicate the involvement of ATPase activity in EsxAB substrate translocation. Read more from Saxena and colleagues on pages 1559–1579
Research Article|
July 21 2022
Identification of ELK1 interacting peptide segments in the androgen receptor
Claire Soave
;
Claire Soave
Data curation, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing - original draft
1Department of Oncology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, MI, U.S.A.
Search for other works by this author on:
Charles Ducker;
Charles Ducker
Data curation, Formal analysis, Validation, Methodology, Writing - review & editing
2School of Life Sciences, University of Nottingham, Queens Medical Centre, Nottingham, U.K.
Search for other works by this author on:
Seongho Kim;
Seongho Kim
Formal analysis
1Department of Oncology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, MI, U.S.A.
Search for other works by this author on:
Thomas Strahl;
Thomas Strahl
Validation
2School of Life Sciences, University of Nottingham, Queens Medical Centre, Nottingham, U.K.
Search for other works by this author on:
Rayna Rosati;
Rayna Rosati
Methodology
1Department of Oncology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, MI, U.S.A.
Search for other works by this author on:
Yanfang Huang;
Yanfang Huang
Data curation, Methodology
1Department of Oncology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, MI, U.S.A.
Search for other works by this author on:
Peter E. Shaw;
Peter E. Shaw
Conceptualization, Resources, Supervision, Funding acquisition, Project administration, Writing - review & editing
2School of Life Sciences, University of Nottingham, Queens Medical Centre, Nottingham, U.K.
Search for other works by this author on:
Manohar Ratnam
Conceptualization, Resources, Formal analysis, Supervision, Funding acquisition, Methodology, Writing - original draft, Project administration
1Department of Oncology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, MI, U.S.A.
Correspondence: Manohar Ratnam (ratnamm@karmanos.org)
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
June 07 2022
Revision Received:
June 29 2022
Accepted:
July 01 2022
Accepted Manuscript online:
July 04 2022
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2022
Biochem J (2022) 479 (14): 1519–1531.
Article history
Received:
June 07 2022
Revision Received:
June 29 2022
Accepted:
July 01 2022
Accepted Manuscript online:
July 04 2022
Citation
Claire Soave, Charles Ducker, Seongho Kim, Thomas Strahl, Rayna Rosati, Yanfang Huang, Peter E. Shaw, Manohar Ratnam; Identification of ELK1 interacting peptide segments in the androgen receptor. Biochem J 29 July 2022; 479 (14): 1519–1531. doi: https://doi.org/10.1042/BCJ20220297
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.