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Nucleophosmin acts as a novel AP2α‐binding transcriptional corepressor during cell differentiation
Author(s) -
Liu Hsuan,
Tan Bertrand ChinMing,
Tseng Kai Hung,
Chuang Ching Ping,
Yeh ChunWei,
Chen KwangDen,
Lee ShengChung,
Yung Benjamin YatMing
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400909
Subject(s) - corepressor , nucleophosmin , biology , transcriptional regulation , retinoic acid , transcription factor , chromatin , microbiology and biotechnology , psychological repression , histone , genetics , gene , gene expression , repressor
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.