Journal
FEBS LETTERS
Volume 588, Issue 5, Pages 692-700Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2014.01.040
Keywords
Vaccinia-related kinase 1 p53; Interaction; Phosphorylation; DNA damage
Funding
- Ministerio de Ciencia e Innovacion
- JAE-CSIC-Fondo Social Europeo fellowships
- Ministerio de Educacion, Ciencia e Innovacion [SAF2010-14935, CSD2007-0017]
- Kutxa-Fundacion Inbiomed
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DNA damage immediate cellular response requires the activation of p53 by kinases. We found that p53 forms a basal stable complex with VRK1, a Ser-Thr kinase that responds to UV-induced DNA damage by specifically phosphorylating p53. This interaction takes place through the p53 DNA binding domain, and frequent DNA-contact mutants of p53, such as R273H, R248H or R280K, do not disrupt the complex. UV-induced DNA damage activates VRK1, and is accompanied by phosphorylation of p53 at Thr-18 before it accumulates. We propose that the VRK1-p53 basal complex is an early-warning system for immediate cellular responses to DNA damage. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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