Novel insights into Chk1 regulation by phosphorylation.
Checkpoint kinase 1 (Chk1) is a conserved protein kinase central to the cell-cycle checkpoint during DNA damage response (DDR). Until recently, ATR, a protein kinase activated in response to DNA damage or stalled replication, has been considered as the sole regulator of Chk1. Recent progress, however, has led to the identification of additional protein kinases involved in Chk1 phosphorylation, affecting the subcellular localization and binding partners of Chk1. In fact, spatio-temporal regulation of Chk1 is of critical importance not only in the DDR but also in normal cell-cycle progression. In due course, many potent inhibitors targeted to Chk1 have been developed as anticancer agents and some of these inhibitors are currently in clinical trials. In this review, we summarize the current knowledge of Chk1 regulation by phosphorylation.
Division of Biochemistry, Aichi Cancer Center Research Institute; Department of Cellular Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Hidemasa
H
Goto
Kousuke
K
Kasahara
Masaki
M
Inagaki
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D000071877:Checkpoint Kinase 1; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
D012694:Serine; D011494:Protein Kinases; D064007:Ataxia Telangiectasia Mutated Proteins; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D018844:Cyclin-Dependent Kinases