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Identification of a potential role of NPM in transcriptional regulation
Author(s) -
Yung Benjamin Yat Ming,
Liu Hsuan,
Tan Bertrand Chin Ming,
Chiu Ya Ming
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.782.8
Subject(s) - nucleophosmin , acetylation , transcriptional regulation , biology , transcription factor , promoter , regulation of gene expression , psychological repression , microbiology and biotechnology , gene expression , gene , genetics
Nucleophosmin/B23 (NPM) is an important nucleolar phosphoprotein with pleiotropic functions in various cellular processes. Its altered expression in tumor cells indicates an intimate link of this protein to tumorigenesis. Exact mechanism underlying NPM‐mediated cell growth control remains largely elusive. Our recent findings have identified a potential but mostly uncharacterized role of NPM in transcriptional regulation. We found that AP‐2α forms complex with NPM during retinoic acid (RA)‐induced cell differentiation. AP‐2α recruits NPM to the promoters of certain RA‐responsive genes, such as p120, Hsp60 and b‐Myb, and such binding is concomitant with their transcriptional repression. RNAi suppression of NPM alleviates the negative regulation of gene expression exerted by RA treatment. Furthermore, we found that NPM binds to the initiation site of PCNA promoter. C‐terminal site of NPM is critical in activation of PCNA promoter. Acetylation mutations at c‐terminal block NPM‐activated promoter activity. Acetylated NPM mutants that could not activate PCNA promoter are not recruited to the promoter. NPM enhances acetylation‐dependent PCNA transcription in conjunction with histone H4 acetylation. These studies underscore the functional significance of NPM in controlling cell growth and differentiation, and delineate a novel mechanism by which nucleophosmin/B23 may exert such regulatory role.