The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Modulation of Androgen Receptor Activation Function 2 by Testosterone and Dihydrotestosterone
Open accessAbstract
The androgen receptor (AR) is transcriptionally activated by high affinity binding of testosterone (T) or its 5alpha-reduced metabolite, dihydrotestosterone (DHT), a more potent androgen required for male reproductive tract development. The molecular basis for the weaker activity of T was investigated by determining T-bound ligand binding domain crystal structures of wild-type AR and a prostate cancer somatic mutant complexed with the AR FXXLF or coactivator LXXLL peptide. Nearly identical interactions of T and DHT in the AR ligand binding pocket correlate with similar rates of dissociation from an AR fragment containing the ligand binding domain. However, T induces weaker AR FXXLF and coactivator LXXLL motif interactions at activation function 2 (AF2). Less effective FXXLF motif binding to AF2 accounts for faster T dissociation from full-length AR. T can nevertheless acquire DHT-like activity through an AR helix-10 H874Y prostate cancer mutation. The Tyr-874 mutant side chain mediates a new hydrogen bonding scheme from exterior helix-10 to backbone protein core helix-4 residue Tyr-739 to rescue T-induced AR activity by improving AF2 binding of FXXLF and LXXLL motifs. Greater AR AF2 activity by improved core helix interactions is supported by the effects of melanoma antigen gene protein-11, an AR coregulator that binds the AR FXXLF motif and targets AF2 for activation. We conclude that T is a weaker androgen than DHT because of less favorable T-dependent AR FXXLF and coactivator LXXLL motif interactions at AF2.
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Cites
The Androgen Axis in Recurrent Prostate Cancer
Mohler, J. L., Gregory, C. W., Ford, O. H., Kim, D., Weaver, C. M., Petrusz, P., Wilson, E. M., & French, F. S. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-1146-03 · Cited by 675
Self-citationWärnmark, A., Treuter, E., Wright, A. P. H., & Gustafsson, J.-A. (2003) · Molecular Endocrinology · doi:10.1210/me.2002-0384 · Cited by 308
Pereira de Jésus‐Tran, K., Côté, P., Cantin, L., Blanchet, J., Labrie, F., & Breton, R. (2006) · Protein Science · doi:10.1110/ps.051905906 · Cited by 278
Langley, E., Kemppainen, J. A., & Wilson, E. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.1.92 · Cited by 233
Self-citationPersistent Intraprostatic Androgen Concentrations after Medical Castration in Healthy Men
Page, S. T., Lin, D. W., Mostaghel, E. A., Hess, D. L., True, L. D., Amory, J. K., Nelson, P. S., Matsumoto, A. M., & Bremner, W. J. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0968 · Cited by 229
Schaufele, F., Carbonell, X., Guerbadot, M., Borngraeber, S., Chapman, M. S., Ma, A. A. K., Miner, J. N., & Diamond, M. I. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408819102 · Cited by 208
Hsu, C.-L., Chen, Y.-L., Yeh, S., Ting, H.-J., Hu, Y.-C., Lin, H., Wang, X., & Chang, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211908200 · Cited by 85
Cited by
The role of androgen receptor mutations in prostate cancer progression.
Brooke, G., & Bevan, C. (2009) · Current Genomics · doi:10.2174/138920209787581307 · Cited by 181
Androgen receptor coregulators: recruitment via the coactivator binding groove
van de Wijngaart, D. J., Dubbink, H. J., van Royen, M. E., Trapman, J., & Jenster, G. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.08.007 · Cited by 122
Structural analyses of sex hormone-binding globulin reveal novel ligands and function
Avvakumov, G. V., Cherkasov, A., Muller, Y. A., & Hammond, G. L. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.09.005 · Cited by 91
Brooke, G. N., Parker, M. G., & Bevan, C. L. (2008) · Oncogene · doi:10.1038/sj.onc.1210955 · Cited by 79
Regulation of androgen action during establishment of pregnancy
Gibson, D. A., Simitsidellis, I., & Saunders, P. T. K. (2016) · Journal of Molecular Endocrinology · doi:10.1530/jme-16-0027 · Cited by 42
Metadata
- Authors
- Askew, E. B., Gampe, R. T., Stanley, T. B., Faggart, J. L., & Wilson, E. M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-08
- Volume
- 282
- Issue
- 35
- Pages
- 25801-25816
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2066225075
- Cited by
- 210
- References
- 7
- FWCI
- 13.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Askew, E. B., Gampe, R. T., Stanley, T. B., Faggart, J. L., & Wilson, E. M. (2007). Modulation of Androgen Receptor Activation Function 2 by Testosterone and Dihydrotestosterone. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m703268200
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
