P15RS/RPRD1A (p15INK4b-related sequence/regulation of nuclear pre-mRNA domain-containing protein 1A) interacts with HDAC2 in inhibition of the Wnt/β-catenin signaling pathway

Chunxiao Liu, Yanquan Zhang, Jun Li, Yinyin Wang, Fangli Ren, Yifan Zhou, Yinyuan Wu, Yarui Feng, Yu Zhou, Fuqin Su, Baoqing Jia, Dong Wang, Zhijie Chang

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

We previously reported that p15RS (p15INK4b-related sequence), a regulation of nuclear pre-mRNA domain containing protein, inhibited Wnt signaling by interrupting the formation of the β-catenin•TCF4 complex. However, how p15RS functions as an intrinsic repressor to repress transcription remains unclear. Inthis study,weshowthatp15RS,througha specific interaction with HDAC2 (histone deacetylase 2), a deacetylase that regulates gene transcription, maintains histone H3 in a deacetylated state in the promoter region of Wnt-targeted genes where β-catenin•TCF4 is bound. We observed that histone deacetylase inhibitors impair the ability of p15RS in inhibiting Wnt/β-catenin signaling. Depletion of HDAC2 markedly disabled p15RS inhibition ofWnt/β-catenin-mediated transcription. Interestingly, overexpression of p15RS decreases the level of acetylated histoneH3in the c-MYC promoter. Finally, we demonstrate that p15RS significantlyenhancesthe association ofHDAC2andTCF4andenhances the occupancy ofHDAC2to DNA, resulting in the deacetylation of histone H3 and the failure of β-catenin interaction. We propose that p15RS acts as an intrinsic transcriptional repressor for Wnt/ β-catenin-mediated gene transcription at least partially through recruiting HDAC2 to occupy the promoter and maintaining deacetylated histone H3.

Original languageEnglish
Pages (from-to)9701-9713
Number of pages13
JournalJournal of Biological Chemistry
Volume290
Issue number15
DOIs
StatePublished - Apr 10 2015

Bibliographical note

Publisher Copyright:
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'P15RS/RPRD1A (p15INK4b-related sequence/regulation of nuclear pre-mRNA domain-containing protein 1A) interacts with HDAC2 in inhibition of the Wnt/β-catenin signaling pathway'. Together they form a unique fingerprint.

Cite this