Abstract
The transcription factor Miz1 is required for DNA-damage-induced cell-cycle arrest. We have now identified 14-3-3eta as a gene that inhibits Miz1 function through interaction with its DNA binding domain. Binding of 14-3-3eta to Miz1 depends on phosphorylation by Akt and regulates the recovery of cells from arrest after DNA damage. Miz1 has two functions in response to DNA damage: first, it is required for upregulation of a large group of genes, a function that is regulated by c-Myc, but not by 14-3-3eta; second, Miz1 represses the expression of many genes in response to DNA damage in an Akt- and 14-3-3eta-regulated manner.
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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Animals
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Cell Cycle / physiology*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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DNA Damage / genetics*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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DNA-Binding Proteins / physiology
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Gene Expression Regulation / physiology
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Gene Library
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HeLa Cells
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Humans
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Kruppel-Like Transcription Factors
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Mice
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Molecular Sequence Data
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NIH 3T3 Cells
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Phosphorylation
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Protein Binding / physiology
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Protein Structure, Tertiary / physiology
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism
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Rats
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Up-Regulation / physiology
Substances
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14-3-3 Proteins
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Cell Cycle Proteins
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DNA-Binding Proteins
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Kruppel-Like Transcription Factors
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MYC protein, human
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-myc
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Transcription Factors
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YWHAH protein, human
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ZBTB17 protein, human
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AKT1 protein, human
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Akt1 protein, rat
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt