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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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14-3-3 Proteins / genetics*
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14-3-3 Proteins / metabolism
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3' Untranslated Regions
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AU Rich Elements
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Antineoplastic Agents / pharmacology
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Apoptosis
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Biomarkers, Tumor / genetics*
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Biomarkers, Tumor / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle Checkpoints*
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Cell Line, Tumor
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Cisplatin / pharmacology
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Exoribonucleases / genetics*
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Exoribonucleases / metabolism
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Gene Expression Regulation, Neoplastic
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Humans
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Microarray Analysis
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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RNA-Binding Proteins
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Tumor Suppressor Protein p53 / metabolism*
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fas Receptor / genetics*
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fas Receptor / metabolism
Substances
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14-3-3 Proteins
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3' Untranslated Regions
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Antineoplastic Agents
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Biomarkers, Tumor
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Carrier Proteins
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FAS protein, human
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Nuclear Proteins
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RNA-Binding Proteins
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TP53 protein, human
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Tumor Suppressor Protein p53
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ZMAT3 protein, human
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fas Receptor
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Exoribonucleases
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SFN protein, human
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Cisplatin