p53 downregulates Down syndrome-associated DYRK1A through miR-1246 |
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Authors: | Zhang Yu Liao Jun-Ming Zeng Shelya X Lu Hua |
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Affiliation: | Department of Biochemistry & Molecular Biology, Indiana University School of Medicine-Simon Cancer Center, 635 Barnhill Drive, MS4053, Indianapolis, Indiana 46202, USA. |
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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. |
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Keywords: | miR‐1246 p53 DYRK1A Down syndrome NFATc1 |
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