Research Paper Volume 10, Issue 11 pp 3308—3326
ZNF185 is a p53 target gene following DNA damage
- 1 Department of Experimental Medicine, TOR, University of Rome “Tor Vergata”, Rome 00133, Italy
- 2 Department of Systems Medicine, University of Rome “Tor Vergata”, Rome 00133, Italy
- 3 Istituto Dermopatico dell’Immacolata-IRCCS, Rome 00163, Italy
- 4 MRC-Toxicology Unit, University of Cambridge, Cambridge, UK
Received: August 10, 2018 Accepted: November 1, 2018 Published: November 16, 2018
https://doi.org/10.18632/aging.101639How to Cite
Copyright: Smirnov et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The transcription factor p53 is a key player in the tumour suppressive DNA damage response and a growing number of target genes involved in these pathways has been identified. p53 has been shown to be implicated in controlling cell motility and its mutant form enhances metastasis by loss of cell directionality, but the p53 role in this context has not yet being investigated. Here, we report that ZNF185, an actin cytoskeleton-associated protein from LIM-family of Zn-finger proteins, is induced following DNA-damage. ChIP-seq analysis, chromatin crosslinking immune-precipitation experiments and luciferase assays demonstrate that ZNF185 is a bona fide p53 target gene. Upon genotoxic stress, caused by DNA-damaging drug etoposide and UVB irradiation, ZNF185 expression is up-regulated and in etoposide-treated cells, ZNF185 depletion does not affect cell proliferation and apoptosis, but interferes with actin cytoskeleton remodelling and cell polarization. Bioinformatic analysis of different types of epithelial cancers from both TCGA and GTEx databases showed a significant decrease in ZNF185 mRNA level compared to normal tissues. These findings are confirmed by tissue micro-array IHC staining. Our data highlight the involvement of ZNF185 and cytoskeleton changes in p53-mediated cellular response to genotoxic stress and indicate ZNF185 as potential biomarker for epithelial cancer diagnosis.
Abbreviations
LIM domain: Lin-l 1, Isl-1 and Mec-3 domain; bs: binding site; TMA: tissue micro-array; ChIP: chromatin immuno-precipitation; cBCC: cutaneous basal cell carcinoma; cSCC: cutaneous squamous cell carcinoma; cMM: cutaneous malignant melanoma.