VRK1 interacts with p53 forming a basal complex that is activated by UV-induced DNA damage

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• 作者：Inmaculada L贸pez-S谩nchez ; Alberto Valbuena ; Marta V谩zquez-Cedeira ; Jyoti Khadake ; Marta Sanz-Garc铆a ; Alej ; ro Carrillo-Jim茅nez ; Pedro A. Lazo
• 关键词：VRK1 ; vaccinia-related kinase 1 ; DDR ; DNA damage response ; UV ; ultraviolet light ; DBD ; DNA binding domain
• 刊名：FEBS Letters
• 出版年：3 March, 2014
• 年：2014
• 卷：588
• 期：5
• 页码：692-700
• 全文大小：1403 K

文摘

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.