Distinct roles for JNK1 and JNK3 during TNF-alpha- or etoposide-induced apoptosis in HeLa cells.
Here, we show that JNK1 and JNK3 have different roles in TNF-alpha- or etoposide-induced apoptosis in HeLa cells. Dominant negative JNK1 inhibited TNF-alpha- or etoposide-induced apoptosis, while dominant negative JNK3 promoted TNF-alpha- or etoposide-induced apoptosis. During TNF-alpha-induced apoptosis, JNK1 was activated in a biphasic manner, exhibiting both transient and sustained activity, whereas JNK3 was activated early and in a transient manner. The role of JNK3 activation was an anti-apoptotic effect, while the role of JNK1 activation was a pro-apoptotic effect. These results suggest that the anti-apoptotic mechanism of JNK3 in TNF-alpha-induced apoptosis originates before the apoptotic machinery is triggered.
Ham
Young-Mi
YM
Division of Pharmaceutical Biosciences, College of Pharmacy and the Research Institute for Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, Korea.
Lim
Jin-Hee
JH
Lee
Seung-Ki
SK
D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death; D005047:Etoposide / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D005047:Etoposide; D048057:Mitogen-Activated Protein Kinase 10; D048055:Mitogen-Activated Protein Kinase 8