ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain

Motoko Unoki, Toshihiko Nishidate, Yusuke Nakamura

Research output: Contribution to journalArticlepeer-review

213 Citations (Scopus)

Abstract

ICBP90, inverted CCAAT box-binding protein of 90 kDa, has been reported as a regulator of topoisomerase IIα expression. We present evidence here that ICBP90 binds to methyl-CpG when at least one symmetrically methylated-CpG dinucleotides is presented as its recognition sequence. A SET and RING finger-associated (SRA) domain accounts for the high binding affinity of ICBP90 for methyl-CpG dinucleotides. This protein constitutes a complex with HDAC1 also via its SRA domain, and bound to methylated promoter regions of various tumor suppressor genes, including p16INK4A and p14ARF, in cancer cells. It has been reported that expression of ICBP90 was upregulated by E2F-1, and we confirmed that the upregulation was caused by binding of E2F-1 to the intron1 of ICBP90, which contains two E2F-1-binding motifs. Our data also revealed accumulation of ICBP90 in breast-cancer cells, where it might suppress expression of tumor suppressor genes through deacetylation of histones after recruitment of HDAC1. The data reported here suggest that ICBP90 is involved in cell proliferation by way of methylation-mediated regulation of certain genes.

Original languageEnglish
Pages (from-to)7601-7610
Number of pages10
JournalOncogene
Volume23
Issue number46
DOIs
Publication statusPublished - Oct 7 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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