KAT8 regulates androgen signaling in prostate cancer cells

Ji Young Kim, Jindan Yu, Sarki A. Abdulkadir, Debabrata Chakravarti*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Androgen receptor (AR) plays pivotal roles in prostate cancer. Upon androgen stimulation, AR recruits the Protein kinase N1 (PKN1), which phosphorylates histone H3 at threonine 11, with subsequent recruitment of tryptophan, aspartic acid (WD) repeat-containing protein 5 (WDR5) and the su(var)3–9, enhancer of zeste, trithorax/mixed-lineage leukemia (SET1/MLL) histone methyltransferase complex to promote AR target gene activation and prostate cancer cell growth. However, the underlying mechanisms of target gene activation and cell growth subsequent to WDR5 recruitment are not well understood. Here, we demonstrate an epigenetic cross talk between histone modifications and AR target gene regulation. We discovered that K(lysine) acetyltransferase 8 (KAT8), a member of the MOZ, YBF2/SAS2, and TIP 60 protein 1 (MYST) family of histone acetyltransferases that catalyzes histone H4 lysine 16 acetylation, colocalized with WDR5 at AR target genes, resulting in hormone-dependent gene activation in prostate cancer cells. PKN1 or WDR5 knockdown severely inhibited KAT8 association with AR target genes and histone H4 lysine 16 acetylation upon androgen treatment. Knockdown of KAT8 significantly decreased AR target gene expression and prostate cancer cell proliferation. Collectively, these data describe a trans-histone modification pathway involving PKN1/histone H3 threonine 11 phosphorylation followed by WDR5/MLL histone methyltransferase and KAT8/histone acetyltransferase recruitment to effect androgen-dependent gene activation and prostate cancer cell proliferation.

Original languageEnglish (US)
Pages (from-to)925-936
Number of pages12
JournalMolecular Endocrinology
Volume30
Issue number8
DOIs
StatePublished - Aug 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Fingerprint Dive into the research topics of 'KAT8 regulates androgen signaling in prostate cancer cells'. Together they form a unique fingerprint.

  • Cite this