THE ROLE OF C-JUN N-TERMINAL KINASE (JNK) IN APOPTOSIS INDUCED BY ULTRAVIOLET-C AND GAMMA-RADIATION - DURATION OF JNK ACTIVATION MAY DETERMINE CELL-DEATH AND PROLIFERATION

c-Jun N-terminal kinases (JNKs) participate in cellular responses to m itogenic stimuli, environmental stresses, and apoptotic agents. The me chanisms by which JNK integrates with other signaling pathways and reg ulates the diverse cellular events are unclear. We found JNK, but not p38-mitogen-activated protein kinase (MAPK) or extracellular signal-re gulated kinase 2, to be persistently activated in apoptosis induced by gamma radiation, UV-C, and anti-Fas treatment. Direct correlation was found between JNK activation and apoptosis induced by UV-C and gamma radiation; however, JNK induction and apoptosis induced by Fas signali ng were not well correlated. Overexpression of activated JNK1 caused c ell death in transfected cells, and the expression of a dominant-negat ive mutant of MAPK kinase 1 or JNK1 (but not a dominant-negative mutan t of p38-MAPK or c-Raf) prevented the UV-C- and gamma radiation-induce d cell death. The inductions of JNK in T-cell activation and apoptosis were distinguished by the different activation patterns, transient ve rsus persistent, respectively. Co-treatment with a tyrosine phosphatas e inhibitor (sodium orthovanadate) and T-cell activation signals (phor bol 12-myristate 13-acetate plus ionomycin) prolonged JNK induction, f ollowed by T-cell apoptosis. Our data revealed the requirement of the JNK pathway in radiation-induced apoptosis and implicated the importan ce of the duration of JNK activation in determining the cell fates.