期刊
ONCOGENE
卷 33, 期 35, 页码 4407-4417出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2013.594
关键词
Wig-1; p53; FAS; 14-3-3 sigma; AU-rich element; AU-rich element-binding proteins
资金
- Swedish Cancer Society
- Swedish Research Council (VR)
- Gustaf V Jubilee Fund
- Karolinska Institutet Distinguished Professor award
Wig-1, also known as ZMAT3, is a p53 target gene that encodes an RNA-binding zinc-finger protein involved in the regulation of mRNA stability through binding to AU-rich elements (AREs). We have used microarray analysis to identify novel Wig-1 target mRNAs. We identified 2447 transcripts with >fourfold differential expression between Wig-1 and control small interfering (si) RNA-treated HCT116 cells. Several p53 target genes were among the deregulated transcripts. We found that Wig-1 regulates FAS and 14-3-3 sigma mRNA independently of p53. We show that Wig-1 binds to FAS mRNA 3'-UTR and decreases its stability through an ARE in the 3'-UTR. Depletion of Wig-1 was associated with increased cell death and reduced cell cycle arrest upon DNA damage. Our results suggest a role of Wig-1 as a survival factor that directs the p53 stress response toward cell cycle arrest rather than apoptosis through the regulation of FAS and 14-3-3 sigma mRNA levels.
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