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Cell Death Dis ; 7: e2184, 2016 Apr 07.
Article in English | MEDLINE | ID: mdl-27054339

ABSTRACT

The integrity of the genome is maintained by a host of surveillance and repair mechanisms that are pivotal for cellular function. The tumour suppressor protein p53 is a major component of the DNA damage response pathway and plays a vital role in the maintenance of cell-cycle checkpoints. Here we show that a microRNA, miR-486, and its host gene ankyrin-1 (ANK1) are induced by p53 following DNA damage. Strikingly, the cytoskeleton adaptor protein ankyrin-1 was induced over 80-fold following DNA damage. ANK1 is upregulated in response to a variety of DNA damage agents in a range of cell types. We demonstrate that miR-486-5p is involved in controlling G1/S transition following DNA damage, whereas the induction of the ankyrin-1 protein alters the structure of the actin cytoskeleton and sustains limited cell migration during DNA damage. Importantly, we found that higher ANK1 expression correlates with decreased survival in cancer patients. Thus, these observations highlight ANK1 as an important effector downstream of the p53 pathway.


Subject(s)
Ankyrins/genetics , Ankyrins/metabolism , DNA Damage , Tumor Suppressor Protein p53/metabolism , Up-Regulation/genetics , Actin Cytoskeleton/metabolism , Ankyrins/antagonists & inhibitors , Antibiotics, Antineoplastic/pharmacology , Blotting, Western , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Cell Line , Cell Movement/drug effects , DNA Damage/drug effects , DNA Repair , Doxorubicin/pharmacology , Female , Humans , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , MicroRNAs/metabolism , Microscopy, Fluorescence , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA Interference , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Tumor Suppressor Protein p53/antagonists & inhibitors , Tumor Suppressor Protein p53/genetics
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