We recently described a signal transduction pathway that contributes to androgen receptor (AR) regulation based on site-specific ADP-ribosylation by PARP7, a mono-ADP-ribosyltransferase implicated in several human cancers. ADP-ribosylated AR is recognized by PARP9/DTX3L, a heterodimeric complex that contains an ADP-ribose reader (PARP9) and a ubiquitin E3 ligase (DTX3L). Here, we have characterized the cellular and biochemical requirements for AR ADP-ribosylation by PARP7. We found that the reaction requires nuclear localization of PARP7 and an agonist-induced conformation of AR. PARP7 contains a Cys3His1-type zinc finger (ZF), which also is critical for AR ADP-ribosylation. The Parp7 ZF is required for efficient nuclear import by a nuclear localization signal encoded in PARP7, but rescue experiments indicate the ZF makes a contribution to AR ADP-ribosylation that is separable from the effect on nuclear transport. ZF mutations do not detectably reduce PARP7 catalytic activity and binding to AR, but they do result in the loss of PARP7 enhancement of AR-dependent transcription of the MYBPC1 gene. Our data reveals critical roles for AR conformation and the PARP7 ZF in AR ADP-ribosylation and AR-dependent transcription.
Skip Nav Destination
Article navigation
August 2021
-
Cover Image
Cover Image
The image on the cover of this issue of Biochemical Journal (volume 478, issue 15) shows the crystal structure of the type III kinase inhibitor GSK2850163 bound to IRE1 kinase site, with key structural elements of kinases highlighted. Image courtesy of Langlais et al. (pages 2953–2975).
Research Article|
August 10 2021
PARP7 mono-ADP-ribosylates the agonist conformation of the androgen receptor in the nucleus
Teddy Kamata;
Teddy Kamata
Conceptualization, Resources, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing - original draft, Writing - review & editing
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, U.S.A.
Search for other works by this author on:
Chun-Song Yang;
Chun-Song Yang
Resources, Methodology
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, U.S.A.
Search for other works by this author on:
Bryce M. Paschal
Conceptualization, Resources, Formal analysis, Supervision, Funding acquisition, Validation, Visualization, Methodology, Writing - original draft, Project administration, Writing - review & editing
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, U.S.A.
Correspondence: Bryce M. Paschal (paschal@virginia.edu)
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
May 25 2021
Revision Received:
July 13 2021
Accepted:
July 15 2021
Accepted Manuscript online:
July 15 2021
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2021
Biochem J (2021) 478 (15): 2999–3014.
Article history
Received:
May 25 2021
Revision Received:
July 13 2021
Accepted:
July 15 2021
Accepted Manuscript online:
July 15 2021
Citation
Teddy Kamata, Chun-Song Yang, Bryce M. Paschal; PARP7 mono-ADP-ribosylates the agonist conformation of the androgen receptor in the nucleus. Biochem J 13 August 2021; 478 (15): 2999–3014. doi: https://doi.org/10.1042/BCJ20210378
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.