Abstract
Exposure of colorectal cancer (CRC) cells to ionizing radiation results in a cell-cycle arrest in G1 and G2. The G1 arrest is due to p53-mediated induction of the cyclin-dependent kinase inhibitor p21WAF1/CIP1/SDI1, but the basis for the G2 arrest is unknown. Through a quantitative analysis of gene expression patterns in CRC cell lines, we have discovered that 14-3-3sigma is strongly induced by gamma irradiation and other DNA-damaging agents. The induction of 14-3-3sigma is mediated by a p53-responsive element located 1.8 kb upstream of its transcription start site. Exogenous introduction of 14-3-3sigma into cycling cells results in a G2 arrest. As the fission yeast 14-3-3 homologs rad24 and rad25 mediate similar checkpoint effects, these results document a molecular mechanism for G2/M control that is conserved throughout eukaryotic evolution and regulated in human cells by p53.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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14-3-3 Proteins
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism
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Colorectal Neoplasms*
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / genetics
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Cyclins / metabolism
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DNA Damage / physiology
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Enzyme Inhibitors / metabolism*
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Eukaryotic Cells / cytology
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Eukaryotic Cells / metabolism
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Eukaryotic Cells / radiation effects
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Evolution, Molecular
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Exonucleases*
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Exoribonucleases
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G2 Phase / genetics*
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Gene Expression Regulation, Neoplastic / radiation effects
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Growth Inhibitors / metabolism
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Humans
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In Situ Hybridization, Fluorescence
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Isoenzymes / genetics
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Isoenzymes / metabolism*
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Mitosis / genetics*
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Molecular Sequence Data
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Polyploidy
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Proteins / genetics
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Proteins / metabolism*
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RNA, Messenger / analysis
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Tumor Cells, Cultured / cytology
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Tumor Cells, Cultured / metabolism
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Tumor Cells, Cultured / radiation effects
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Tumor Suppressor Protein p53 / metabolism*
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Tyrosine 3-Monooxygenase*
Substances
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14-3-3 Proteins
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Biomarkers, Tumor
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Enzyme Inhibitors
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Growth Inhibitors
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Isoenzymes
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Neoplasm Proteins
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Proteins
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RNA, Messenger
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Tumor Suppressor Protein p53
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Tyrosine 3-Monooxygenase
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Exonucleases
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Exoribonucleases
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SFN protein, human
Associated data
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GENBANK/AF029081
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GENBANK/AF029082