title: p53 downregulates Down syndrome-associated DYRK1A through miR-1246.
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.
authors.affiliation: Department of Biochemistry & Molecular Biology, Indiana University School of Medicine-Simon Cancer Center, 635 Barnhill Drive, MS4053, Indianapolis, Indiana 46202, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Liao
authors.forename: Shelya X
authors.initials: SX
authors.lastname: Zeng
authors.forename: Hua
authors.initials: H
authors.lastname: Lu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D045325:HCT116 Cells; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D000097603:Dyrk Kinases
chemical_list: D035683:MicroRNAs; D050778:NFATC Transcription Factors; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; D000097603:Dyrk Kinases; C494003:NFATC1 protein, human; C495901:TP53 protein, human