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Wig-1 regulates cell cycle arrest and cell death through the p53 targets FAS and 14-3-3σ
- Source :
- Oncogene
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
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 14-3-3σ 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 14-3-3σ mRNA levels.
- Subjects :
- p53
Cancer Research
Programmed cell death
Cell cycle checkpoint
Antineoplastic Agents
Apoptosis
Biology
AU-rich element-binding proteins
Cell Line, Tumor
Biomarkers, Tumor
Genetics
Humans
Wig-1
fas Receptor
Nuclear protein
3' Untranslated Regions
Molecular Biology
AU Rich Elements
AU-rich element
Microarray analysis techniques
Three prime untranslated region
Nuclear Proteins
RNA-Binding Proteins
Cell Cycle Checkpoints
FAS
Microarray Analysis
Fas receptor
Cell biology
Gene Expression Regulation, Neoplastic
14-3-3 Proteins
Exoribonucleases
Original Article
14-3-3σ
Cisplatin
Tumor Suppressor Protein p53
Carrier Proteins
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....445b85356e9a7c6ec649c399caa63af3