摘要
DNA damage response (DDR) is among the most important of the mechanisms that maintain genome stability which, when destabilized, predisposes organs to cancer. Reversible phosphorylation mediated by protein kinases and protein phosphatases regulates most, if not all, cellular activities, including DDR. Protein kinase inhibitors have become the main focus of targeted therapy and anticancer drug development. However, our limited knowledge of protein phosphatase function is compromising our capacity to develop therapeutic agents against phosphatases. In this review, we summarize the roles of serine/threonine protein phosphatases involved in DDR and propose that in situ dephosphorylation of phosphoproteins by protein phosphatases, instead of proteasome-mediated degradation of phosphoproteins, is mainly employed by cells.
DNA damage response （DDR） is among the most important of the mechanisms that maintain genome stability which, when destabilized, predisposes organs to cancer. Reversible phosphorylation mediated by protein kinases and protein phosphatases regu- lates most, if not all, cellular activities, including DDR. Protein kinase inhibitors have become the main focus of targeted therapy and anticancer drug development. However, our limited knowledge of protein phosphatase function is compromising our capacity to develop therapeutic agents against phosphatases. In this review, we summarize the roles of serine/threonine protein phosphatases involved in DDR and propose that in situ dephosphorylation of phosphoproteins by protein phosphatases, instead of pro- teasome-mediated degradation of phosphoproteins, is mainly employed by cells.
基金
supported by the startup fund from Capital Normal University
the National Natural Science Foundation of China (30570371, 90608014, 30711120570 and 31071190)
the Program for New Century Excellent Talents in University (NCET-06-0187)
Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ200810028014)
the National Basic Research Program of China (2010CB911904)
Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality (PHR20110508) to XU XingZhi
