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, i nitiates apoptosis, or programmed cell death, in many cell systems. Th is mode of radiation-induced cell kill should be distinguished from cl onogenic cell death due to unrepaired DNA damage. Ionizing radiation n ot only exerts its effect on the nuclear DNA, but also at the plasma m embrane level where it may activate multiple signal transduction pathw ays. One of these pathways is the stress-activated protein kinase (SAP K) cascade which transduces death signals from the cell membrane to th e 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-induce d apoptosis may ultimately provide novel strategies of intervention in specific signal transduction pathways to favorably alter the therapeu tic ratio in the treatment of human malignancies. (C) 1998 Elsevier Sc ience Ireland Ltd. All rights reserved.