c­Abl­mediated tyrosine phosphorylation of DNA damage response proteins and implications in important cellular functions (Review).

ABSTRACT

Tyrosine phosphorylation is an essential post­translational protein modification catalyzed by tyrosine kinases. c­Abl is a crucial non­receptor tyrosine kinase, which is most commonly activated by auto­phosphorylation, DNA damage and by interacting with other protein kinases. DNA damage response (DDR) proteins stimulated by DNA lesions or chromatin alterations recruit the DNA repair and cell cycle checkpoint machinery to restore genome integrity and cellular homeostasis. The fundamental roles of activated c­Abl tyrosine kinase in cellular response pathways have been intensively and extensively investigated and in recent years, a number of c­Abl protein binding partners have been determined; however, the functional roles of these molecules remain to be determined. The present review aimed to summarize the DDR proteins phosphorylated by c­Abl tyrosine kinase that have been identified to date, in addition to the functional outcomes of these phosphotyrosine events. Notably, it has been discovered that c­Abl tyrosine kinase can bind with and phosphorylate DDR proteins at different tyrosine sites, which serve distinct roles in various cellular contexts.