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Wig-1 regulates cell cycle arrest and cell death through the p53 targets FAS and 14-3-3?.

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 >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? 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? mRNA levels.

SUBMITTER: Bersani C

PROVIDER: S-EPMC4150987 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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

Bersani C C Xu L-D LD Vilborg A A Lui W-O WO Wiman K G KG

Oncogene 20140127 35

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 ...[more]

PMID: 24469038

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