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Identification of a Novel Coregulator, SH3YL1, That Interacts With the Androgen Receptor N-Terminus.

Publication ,  Journal Article
Blessing, AM; Ganesan, S; Rajapakshe, K; Ying Sung, Y; Reddy Bollu, L; Shi, Y; Cheung, E; Coarfa, C; Chang, JT; McDonnell, DP; Frigo, DE
Published in: Mol Endocrinol
October 2015

Nuclear receptor (NR)-mediated transcriptional activity is a dynamic process that is regulated by the binding of ligands that induce distinct conformational changes in the NR. These structural alterations lead to the differential recruitment of coregulators (coactivators or corepressors) that control the expression of NR-regulated genes. Here, we show that a stretch of proline residues located within the N-terminus of androgen receptor (AR) is a bona fide coregulator binding surface, the disruption of which reduces the androgen-dependent proliferation and migration of prostate cancer (PCa) cells. Using T7 phage display, we identified a novel AR-interacting protein, Src homology 3 (SH3)-domain containing, Ysc84-like 1 (SH3YL1), whose interaction with the receptor is dependent upon this polyproline domain. As with mutations within the AR polyproline domain, knockdown of SH3YL1 attenuated androgen-mediated cell growth and migration. RNA expression analysis revealed that SH3YL1 was required for the induction of a subset of AR-modulated genes. Notable was the observation that ubinuclein 1 (UBN1), a key member of a histone H3.3 chaperone complex, was a transcriptional target of the AR/SH3YL1 complex, correlated with aggressive PCa in patients, and was necessary for the maximal androgen-mediated proliferation and migration of PCa cells. Collectively, these data highlight the importance of an amino-terminal activation domain, its associated coregulator, and downstream transcriptional targets in regulating cellular processes of pathological importance in PCa.

Duke Scholars

Published In

Mol Endocrinol

DOI

EISSN

1944-9917

Publication Date

October 2015

Volume

29

Issue

10

Start / End Page

1426 / 1439

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Transcription Factors
  • Receptors, Androgen
  • Protein Structure, Tertiary
  • Protein Binding
  • Prognosis
  • Peptides
  • Nuclear Proteins
  • Models, Biological
  • Membrane Proteins
 

Citation

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Blessing, A. M., Ganesan, S., Rajapakshe, K., Ying Sung, Y., Reddy Bollu, L., Shi, Y., … Frigo, D. E. (2015). Identification of a Novel Coregulator, SH3YL1, That Interacts With the Androgen Receptor N-Terminus. Mol Endocrinol, 29(10), 1426–1439. https://doi.org/10.1210/me.2015-1079
Blessing, Alicia M., Sathya Ganesan, Kimal Rajapakshe, Ying Ying Sung, Lakshmi Reddy Bollu, Yan Shi, Edwin Cheung, et al. “Identification of a Novel Coregulator, SH3YL1, That Interacts With the Androgen Receptor N-Terminus.Mol Endocrinol 29, no. 10 (October 2015): 1426–39. https://doi.org/10.1210/me.2015-1079.
Blessing AM, Ganesan S, Rajapakshe K, Ying Sung Y, Reddy Bollu L, Shi Y, et al. Identification of a Novel Coregulator, SH3YL1, That Interacts With the Androgen Receptor N-Terminus. Mol Endocrinol. 2015 Oct;29(10):1426–39.
Blessing, Alicia M., et al. “Identification of a Novel Coregulator, SH3YL1, That Interacts With the Androgen Receptor N-Terminus.Mol Endocrinol, vol. 29, no. 10, Oct. 2015, pp. 1426–39. Pubmed, doi:10.1210/me.2015-1079.
Blessing AM, Ganesan S, Rajapakshe K, Ying Sung Y, Reddy Bollu L, Shi Y, Cheung E, Coarfa C, Chang JT, McDonnell DP, Frigo DE. Identification of a Novel Coregulator, SH3YL1, That Interacts With the Androgen Receptor N-Terminus. Mol Endocrinol. 2015 Oct;29(10):1426–1439.

Published In

Mol Endocrinol

DOI

EISSN

1944-9917

Publication Date

October 2015

Volume

29

Issue

10

Start / End Page

1426 / 1439

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Transcription Factors
  • Receptors, Androgen
  • Protein Structure, Tertiary
  • Protein Binding
  • Prognosis
  • Peptides
  • Nuclear Proteins
  • Models, Biological
  • Membrane Proteins