Abstract
Several microRNAs mediate the functions of p53 family members. Here we characterize miR-1246 as a new target of this family. In response to DNA damage, p53 induces the expression of miR-1246 which, in turn, reduces the level of DYRK1A, a Down syndrome-associated protein kinase. Knockdown of p53 has the opposite effect. Overexpression of miR-1246 reduces DYRK1A levels and leads to the nuclear retention of NFATc1, a protein substrate of DYRK1A, and the induction of apoptosis, whereas a miR-1246-specific inhibitor prevented the nuclear import of NFATc1. Together, these results indicate that p53 inhibits DYRK1A expression through the induction of miR-1246.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Apoptosis / genetics
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Cell Line, Tumor
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DNA Damage / genetics
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Down Syndrome / genetics*
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Down Syndrome / metabolism*
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Down-Regulation
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Dyrk Kinases
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HCT116 Cells
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Humans
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / genetics*
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MicroRNAs / metabolism*
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NFATC Transcription Factors / metabolism
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / metabolism*
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / metabolism*
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Tumor Suppressor Protein p53 / genetics*
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Tumor Suppressor Protein p53 / metabolism*
Substances
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MicroRNAs
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NFATC Transcription Factors
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NFATC1 protein, human
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TP53 protein, human
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Tumor Suppressor Protein p53
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases