The role of the stress-activated protein kinase (SAPK/JNK) signaling pathway in radiation-induced apoptosis.
Ionizing radiation, like a variety of other cellular stress factors, initiates apoptosis, or programmed cell death, in many cell systems. This mode of radiation-induced cell kill should be distinguished from clonogenic cell death due to unrepaired DNA damage. Ionizing radiation not only exerts its effect on the nuclear DNA, but also at the plasma membrane level where it may activate multiple signal transduction pathways. One of these pathways is the stress-activated protein kinase (SAPK) cascade which transduces death signals from the cell membrane to the nucleus. This review discusses recent evidence on the critical role of this signaling system in radiation- and stress-induced apoptosis. An improved understanding of the mechanisms involved in radiation-induced apoptosis may ultimately provide novel strategies of intervention in specific signal transduction pathways to favorably alter the therapeutic ratio in the treatment of human malignancies.
Verheij
M
M
Department of Radiotherapy, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam.
Ruiter
G A
GA
Zerp
S F
SF
van Blitterswijk
W J
WJ
Fuks
Z
Z
Haimovitz-Friedman
A
A
Bartelink
H
H
D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000473:pathology; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000473:pathology
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases