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N/C interactions are dispensable for normal in vivo functioning of the androgen receptor in male mice

Sarah El Kharraz, Vanessa Dubois (UGent) , Kaisa-Mari Launonen, Laura Helminen, Jorma J Palvimo, Claude Libert (UGent) , Elien Smeets, Lisa Moris, Roy Eerlings, Dirk Vanderschueren, et al.
(2022) ENDOCRINOLOGY. 163(9).
Author
Organization
Abstract
The androgen receptor (AR) plays a central role in the development and maintenance of the male phenotype. The binding of androgens to the receptor induces interactions between the carboxyterminal ligand-binding domain and the highly conserved 23FQNLF27 motif in the aminoterminal domain. The role of these so-called N/C interactions in AR functioning is debated. In vitro assays show that mutating the AR in the 23FQNLF27 motif (called ARNoC) attenuates the AR transactivation of reporter genes, has no effect on ligand binding, but does affect protein-protein interactions with several AR coregulators. To test the in vivo relevance of the N/C interaction, we analyzed the consequences of the genomic introduction of the ARNoC mutation in mice. Surprisingly, the ARNoC/Y mice show a normal male development, with unaffected male anogenital distance and normal accessory sex glands, male circulating androgen levels, body composition, and fertility. The responsiveness of androgen target genes in kidney, prostate, and testes was also unaffected. We thus conclude that the N/C interactions in the AR are not essential for the development of a male phenotype under normal physiological conditions.
Keywords
Endocrinology, androgen receptor, N, C interaction, mouse model, prostate, male development, MEDIATED TRANSACTIVATION, STRUCTURAL BASIS, TERMINAL DOMAIN, BINDING DOMAIN, MOTIF, PROTEIN, FXXLF, LXXLL, MASS, INTERDOMAIN

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Citation

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MLA
El Kharraz, Sarah, et al. “N/C Interactions Are Dispensable for Normal in Vivo Functioning of the Androgen Receptor in Male Mice.” ENDOCRINOLOGY, vol. 163, no. 9, 2022, doi:10.1210/endocr/bqac104.
APA
El Kharraz, S., Dubois, V., Launonen, K.-M., Helminen, L., Palvimo, J. J., Libert, C., … Claessens, F. (2022). N/C interactions are dispensable for normal in vivo functioning of the androgen receptor in male mice. ENDOCRINOLOGY, 163(9). https://doi.org/10.1210/endocr/bqac104
Chicago author-date
El Kharraz, Sarah, Vanessa Dubois, Kaisa-Mari Launonen, Laura Helminen, Jorma J Palvimo, Claude Libert, Elien Smeets, et al. 2022. “N/C Interactions Are Dispensable for Normal in Vivo Functioning of the Androgen Receptor in Male Mice.” ENDOCRINOLOGY 163 (9). https://doi.org/10.1210/endocr/bqac104.
Chicago author-date (all authors)
El Kharraz, Sarah, Vanessa Dubois, Kaisa-Mari Launonen, Laura Helminen, Jorma J Palvimo, Claude Libert, Elien Smeets, Lisa Moris, Roy Eerlings, Dirk Vanderschueren, Christine Helsen, and Frank Claessens. 2022. “N/C Interactions Are Dispensable for Normal in Vivo Functioning of the Androgen Receptor in Male Mice.” ENDOCRINOLOGY 163 (9). doi:10.1210/endocr/bqac104.
Vancouver
1.
El Kharraz S, Dubois V, Launonen K-M, Helminen L, Palvimo JJ, Libert C, et al. N/C interactions are dispensable for normal in vivo functioning of the androgen receptor in male mice. ENDOCRINOLOGY. 2022;163(9).
IEEE
[1]
S. El Kharraz et al., “N/C interactions are dispensable for normal in vivo functioning of the androgen receptor in male mice,” ENDOCRINOLOGY, vol. 163, no. 9, 2022.
@article{8763626,
  abstract     = {{The androgen receptor (AR) plays a central role in the development and maintenance of the male phenotype. The binding of androgens to the receptor induces interactions between the carboxyterminal ligand-binding domain and the highly conserved 23FQNLF27 motif in the aminoterminal domain. The role of these so-called N/C interactions in AR functioning is debated. In vitro assays show that mutating the AR in the 23FQNLF27 motif (called ARNoC) attenuates the AR transactivation of reporter genes, has no effect on ligand binding, but does affect protein-protein interactions with several AR coregulators. To test the in vivo relevance of the N/C interaction, we analyzed the consequences of the genomic introduction of the ARNoC mutation in mice. Surprisingly, the ARNoC/Y mice show a normal male development, with unaffected male anogenital distance and normal accessory sex glands, male circulating androgen levels, body composition, and fertility. The responsiveness of androgen target genes in kidney, prostate, and testes was also unaffected. We thus conclude that the N/C interactions in the AR are not essential for the development of a male phenotype under normal physiological conditions.}},
  articleno    = {{bqac104}},
  author       = {{El Kharraz, Sarah and Dubois, Vanessa and Launonen, Kaisa-Mari and Helminen, Laura and Palvimo, Jorma J and Libert, Claude and Smeets, Elien and Moris, Lisa and Eerlings, Roy and Vanderschueren, Dirk and Helsen, Christine and Claessens, Frank}},
  issn         = {{0013-7227}},
  journal      = {{ENDOCRINOLOGY}},
  keywords     = {{Endocrinology,androgen receptor,N,C interaction,mouse model,prostate,male development,MEDIATED TRANSACTIVATION,STRUCTURAL BASIS,TERMINAL DOMAIN,BINDING DOMAIN,MOTIF,PROTEIN,FXXLF,LXXLL,MASS,INTERDOMAIN}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{16}},
  title        = {{N/C interactions are dispensable for normal in vivo functioning of the androgen receptor in male mice}},
  url          = {{http://doi.org/10.1210/endocr/bqac104}},
  volume       = {{163}},
  year         = {{2022}},
}
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