DNA damage-activated kinase Chk2 is independent of proliferation or differentiation yet correlates with tissue biology.
The Chk2 kinase is a tumor suppressor and key transducer of DNA-damage checkpoints. We show that the human Chk2 protein is relatively stable, nuclear, and responding to gamma-radiation throughout the cell cycle. Contrary to the retinoblastoma protein-regulated, labile Chk1 kinase restricted to S-G(2) phases, Chk2 remains activatable even in quiescent and differentiating cells. In human tissues, Chk2 is homogeneously expressed in renewing cell populations such as epidermis or intestine, heterogeneous in conditionally renewing tissues, and absent or cytoplasmic in static tissues such as muscle or brain. These data highlight striking differences between Chk2 and Chk1 and show unexpected correlation of Chk2 expression with tissue biology.
Lukas
C
C
Institute of Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen, Denmark.
Bartkova
J
J
Latella
L
L
Falck
J
J
Mailand
N
N
Schroeder
T
T
Sehested
M
M
Lukas
J
J
Bartek
J
J
D000911:Antibodies, Monoclonal; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D064447:Checkpoint Kinase 2; D004249:DNA Damage / Q000502:physiology*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D016193:G1 Phase / Q000502:physiology; D006801:Humans; D012516:Osteosarcoma / Q000201:enzymology / Q000473:pathology; D011494:Protein Kinases / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D016196:S Phase / Q000502:physiology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases