Coactivator MYST1 regulates nuclear factor-κB and androgen receptor functions during proliferation of prostate cancer cells

Anbalagan Jaganathan, Pratima Chaurasia, Guang Qian Xiao, Marc Philizaire, Xiang Lv, Shen Yao, Kerry L. Burnstein, De Pei Liu, Alice C. Levine, Shiraz Mujtaba

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

In prostate cancer (PCa), the functional synergy between androgen receptor (AR) and nuclear factor-κ B (NF-κB) escalates the resistance to therapeutic regimens and promotes aggressive tumor growth. Although the underlying mechanisms are less clear, gene regulatory abilities of coactivators can bridge the transcription functions of AR and NF-κB. The present study shows that MYST1 (MOZ, YBF2 and SAS2, and TIP60 protein 1) costimulates AR and NF-κB functions in PCa cells. We demonstrate that activation of NF-κB promotes deacetylation of MYST1 by sirtuin 1. Further, the mutually exclusive interactions of MYST1 with sirtuin 1 vs AR regulate the acetylation of lysine 16 on histone H4. Notably, in AR-lacking PC3 cells and in AR-depleted LNCaP cells, diminution of MYST1 activates the cleavage of poly(ADP-ribose) polymerase and caspase 3 that leads to apoptosis. In contrast, in AR-transformed PC3 cells (PC3-AR), depletion of MYST1 induces cyclin-dependent kinase (CDK) N1A/p21, which results in G2M arrest. Concomitantly, the levels of phospho-retinoblastoma, E2F1, CDK4, and CDK6 are reduced. Finally, the expression of tumor protein D52 (TPD52) was unequivocally affected in PC3, PC3-AR, and LNCaP cells. Taken together, the results of this study reveal that the functional interactions of MYST1 with AR and NF-κB are critical for PCa progression.

Original languageEnglish (US)
Pages (from-to)872-885
Number of pages14
JournalMolecular Endocrinology
Volume28
Issue number6
DOIs
StatePublished - Jun 2014

    Fingerprint

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Jaganathan, A., Chaurasia, P., Xiao, G. Q., Philizaire, M., Lv, X., Yao, S., Burnstein, K. L., Liu, D. P., Levine, A. C., & Mujtaba, S. (2014). Coactivator MYST1 regulates nuclear factor-κB and androgen receptor functions during proliferation of prostate cancer cells. Molecular Endocrinology, 28(6), 872-885. https://doi.org/10.1210/me.2014-1055