title: Novel regulation of checkpoint kinase 1: Is checkpoint kinase 1 a good candidate for  anti-cancer therapy?
abstract: DNA-damaging strategies, such as radiotherapy and the majority of chemotherapeutic therapies, are the most frequently used non-surgical anti-cancer therapies for human cancers. These therapies activate DNA damage/replication checkpoints, which induce cell-cycle arrest to provide the time needed to repair DNA damage. Due to genetic defect(s) in the ATM (ataxia-telangiectasia mutated)-Chk2-p53 pathway, an ATR (ATM- and Rad3-related)-Chk1-Cdc25 route is the sole checkpoint pathway in a majority of cancer cells. Chk1 inhibitors are expected to selectively induce the mitotic cell death (mitotic catastrophe) of cancer cells. However, recent new findings have pointed out that Chk1 is essential for the maintenance of genome integrity even during unperturbed cell-cycle progression, which is controlled by a variety of protein kinases. These observations have raised concerns about a possible risk of Chk1 inhibitors on the clinics. In this review, we summarize recent advances in Chk1 regulation by phosphorylation, and discuss Chk1 as a molecular target for cancer therapeutics.
authors.affiliation: Division of Biochemistry, Aichi Cancer left Research Institute, Nagoya, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Goto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Izawa
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Masaki
authors.initials: M
authors.lastname: Inagaki
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D064007:Ataxia Telangiectasia Mutated Proteins; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism*; D000071877:Checkpoint Kinase 1; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020687:cdc25 Phosphatases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D011494:Protein Kinases; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases