VRK1 interacts with p53 forming a basal complex that is activated by UV-induced DNA damage |
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| Authors: | Inmaculada López-Sánchez Alberto Valbuena Marta Vázquez-Cedeira Jyoti Khadake Marta Sanz-García Alejandro Carrillo-Jiménez Pedro A Lazo |
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| Institution: | 1. Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Salamanca, Salamanca, Spain;2. Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Salamanca, Spain;3. European Bioinformatics Institute-EMBL, Cambridge, England, United Kingdom |
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| Abstract: | 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. |
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| Keywords: | VRK1 vaccinia-related kinase 1 DDR DNA damage response UV ultraviolet light DBD DNA binding domain |
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