p38 and Chk1 kinases: different conductors for the G(2)/M checkpoint symphony.
The mechanism controlling G(2)/M checkpoint activation after DNA damage was thought to be mediated primarily by nuclear Chk1/Chk2 kinases. Recent evidence indicates that this checkpoint is more complex, involving at least two different biochemical systems that target the Cdc25B and Cdc25C phosphatases. Following genotoxic stress, different kinases integrate signaling from the damaged DNA and other damaged cellular components to regulate Cdc25 inactivation. Our current model for G(2)/M checkpoint activation after genotoxic stress is discussed emphasizing the roles for Chk1 and p38 kinases in checkpoint regulation.
Bulavin
Dmitry V
DV
Gene Response Section, Center for Cancer Research, NCI, NIH, Bethesda, Maryland 20892-4255, USA.
Amundson
Sally A
SA
Fornace
Albert J
AJ
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D000071877:Checkpoint Kinase 1; D004249:DNA Damage; D016195:G2 Phase; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000502:physiology*; D008938:Mitosis; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases
D018797:Cell Cycle Proteins; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases