Chk1 versus Cdc25: chking one's levels of cellular proliferation.
This review summarizes recent studies which have provided new insight into the mechanisms by which the DNA damage response kinase, Chk1 inhibits the dual specificity phosphatase, Cdc25, and thereby regulates cell cycle progression. Recently, Chk1 has been shown to not only regulate Cdc25A degradation but also its ability to interact with various Cdk complexes through phosphorylation of the carboxy-terminus of the phosphatase. Surprisingly, these effects appear to be specific for Chk1, but not Chk2, which may explain the recently reported in vivo haploinsufficiency phenotype observed in the mammary gland using a Chk1 conditional mouse model.
Baylor College of Medicine, Department of Molecular and Cellular Biology, Interdepartmental Program in Cellular and Molecular Biology, Houston, Texas 77030, USA.
Michael H
MH
Lam
Jeffrey M
JM
Rosen
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D000071877:Checkpoint Kinase 1; D002986:Clinical Trials as Topic; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011494:Protein Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D019311:Staurosporine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D020687:cdc25 Phosphatases / Q000378:metabolism*
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; C054852:7-hydroxystaurosporine; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; C000605869:Chek1 protein, mouse; C517009:CDC25C protein, human; C517010:Cdc25c protein, mouse; D020687:cdc25 Phosphatases; D019311:Staurosporine