Nucleophosmin acts as a novel AP2α-binding transcriptional corepressor during cell differentiation

Hsuan Liu, Bertrand Chin Ming Tan, Kai Hung Tseng, Ching Ping Chuang, Chun Wei Yeh, Kwang Den Chen, Sheng Chung Lee, Yat Ming Yung

Research output: Journal article publicationJournal articleAcademic researchpeer-review

53 Citations (Scopus)

Abstract

Nucleophosmin (NPM) is an important nucleolar phosphoprotein with pleiotropic functions in various cellular processes. In this study, we have further examined the largely uncharacterized role of NPM in transcriptional regulation by uncovering novel NPM-binding transcriptional factors. Among potential interactors, we found that activating protein transcription factor 2 (AP2)α forms a complex with NPM during retinoic-acid-induced cell differentiation. We show that this complex is recruited to the promoters of certain retinoic-acid-responsive genes, including NPM itself. Such binding of AP2α, and consequent recruitment of NPM, is selective and dependent on a consensus AP2α-binding sequence. Remarkably, suppression of NPM by RNA interference alleviates the repression of gene expression mediated by retinoic acid and AP2α. Our findings further show that, on promoter binding, NPM probably exerts its repressive effect by inducing a change in local chromatin structure that also engages histone deacetylases. This study unveils a hitherto unrecognized transcriptional corepressor function of the NPM protein, and highlights a novel mechanism by which NPM regulates cell growth and differentiation.
Original languageEnglish
Pages (from-to)394-400
Number of pages7
JournalEMBO Reports
Volume8
Issue number4
DOIs
Publication statusPublished - 1 Apr 2007
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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