Chk1 and Chk2 kinases in checkpoint control and cancer.
Accumulation of mutations and chromosomal aberrations is one of the hallmarks of cancer cells. This enhanced genetic instability is fueled by defects in the genome maintenance mechanisms including DNA repair and cell cycle checkpoint pathways. Here, we discuss the emerging roles of the mammalian Chk1 and Chk2 kinases as key signal transducers within the complex network of genome integrity checkpoints, as candidate tumor suppressors disrupted in sporadic as well as some hereditary malignancies and as potential targets of new anticancer therapies.
Bartek
Jiri
J
Department of Cell Cycle and Cancer, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark. bartek@biobase.dk
Lukas
Jiri
J
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism; D002453:Cell Cycle; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D003110:Colonic Neoplasms / Q000201:enzymology; D004260:DNA Repair; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; C000605869:Chek1 protein, mouse; C578633:Chek2 protein, mouse; D017346:Protein Serine-Threonine Kinases