The cytoskeleton adaptor protein ankyrin-1 is upregulated by p53 following DNA damage and alters cell migration

Hall, A. E., Lu, W.-T., Godfrey, J. D., Antonov, A. V., Paicu, C., Moxon, S., Dalmay, T., Wilczynska, A., Muller, P. A. J. and Bushell, M. (2016) The cytoskeleton adaptor protein ankyrin-1 is upregulated by p53 following DNA damage and alters cell migration. Cell Death and Disease, 7(4), e2184. (doi: 10.1038/cddis.2016.91) (PMID:27054339) (PMCID:PMC4855670)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bushell, Professor Martin
Authors: Hall, A. E., Lu, W.-T., Godfrey, J. D., Antonov, A. V., Paicu, C., Moxon, S., Dalmay, T., Wilczynska, A., Muller, P. A. J., and Bushell, M.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cell Death and Disease
Publisher:Nature Publishing Group
ISSN:2041-4889
ISSN (Online):2041-4889
Published Online:07 April 2016
Copyright Holders:Copyright © 2016 Macmillan Publishers Limited
First Published:First published in Cell Death and Disease 7(4): e2184
Publisher Policy:Reproduced under a Creative Commons License

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