Wig-1 regulates cell cycle arrest and cell death through the p53 targets fas and 14-3-3σ

Abstract

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 4fourfold differential expression between Wig-1 and control small interfering (si)RNAtreated HCT116 cells. Several p53 target genes were among the deregulated transcripts. We found that Wig-1 regulates FAS and 14-3-3σ mRNA independently of p53. We show that Wig-1 binds to FAS mRNA 30-UTR and decreases its stability through an ARE in the 30-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 direct. © 2014 Macmillan Publishers Limited.