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p53 downregulates Down syndrome‐associated DYRK1A through miR‐1246
Author(s) -
Zhang Yu,
Liao JunMing,
Zeng Shelya X,
Lu Hua
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2011.98
Subject(s) - dyrk1a , gene knockdown , microrna , nuclear export signal , nuclear protein , apoptosis , chemistry , p53 protein , microbiology and biotechnology , cancer research , biology , kinase , cell nucleus , gene , biochemistry , nucleus , transcription factor
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.