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Molecular and functional characterization of a new tumor suppressor protein ZNF509 in the regulation of cell growth
Author(s) -
Jeon BuNam,
Yoon JaeHyeon,
Hur ManWook
Publication year - 2010
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.24.1_supplement.678.9
Subject(s) - biology , transcription factor , gene knockdown , cell growth , activator (genetics) , cell cycle , microbiology and biotechnology , tumor suppressor gene , transcription (linguistics) , promoter , suppressor , e2f1 , transcriptional regulation , gene , regulation of gene expression , cell cycle checkpoint , gene expression , carcinogenesis , genetics , linguistics , philosophy
A variety of cellular biological functions like cell proliferation are precisely controlled by a number of protein‐protein interactions among regulatory proteins. In cancer cells, aberrant expression of oncogenes or/and tumor suppressor genes causes dramatic changes in the cellular regulatory program governing cell proliferation. Recently, POK family transcription factors were characterized as critical oncogenes or tumor suppressors that could regulate expression of cell cycle control genes. We found that a novel POK family transcription factor, ZNF509, is induced by p53 and may be a tumor suppressor. ZNF509 is a potent transcriptional activator of CDKN1A encoding cell cycle arrest gene, p21. EMSA, oligo pull‐down, and ChIP assays showed that ZNF509 directly binds to proximal promoter region of p21 in vitro and in vivo. Also ZNF509 and MIZ‐1 interact with each other and synergistically activate transcription of p21 gene. The molecular interaction recruits more co‐activator p300 to the p21 proximal promoter. The ZNF509‐MIZ‐1‐p300 complex acetylates histone Ac‐H3 and ‐H4 at the p21 proximal promoter. Knockdown of endogenous ZNF509 expression results in decrease in the transcription of p21 gene, which increases cell proliferation and DNA synthesis. Overall, our data suggest that ZNF509 is a potent transcription activator of the cell cycle arrest gene p21 and may be a tumor suppressor gene.