Mammalian Ste20-like protein kinase 3 induces a caspase-independent apoptotic pathway.
In this study, it was shown that the mammalian sterile 20-like serine/threonine protein kinase 3 (Mst3) plays an essential role in the staurosporine-induced apoptosis of HeLa cells. The staurosporine-induced apoptosis was reduced by around 65% by the selective knockdown of Mst3 in stable clones, HeLa(siMst3). Although caspases were shown to be involved in the Mst3-mediated apoptosis, only 15-20% of staurosporine-induced apoptosis was suppressed by the caspase inhibitor, z-DEVD-fmk. Accordingly, Mst3 was proposed to trigger a caspase-independent apoptotic pathway in response to staurosporine. Interestingly, staurosporine greatly induced the mitochondrial membrane potential transition in HeLa cells, but had no effect in Hela(siMst3). The role of Mst3 in controlling the mitochondrial integrity was therefore proposed, presumably through the regulation of Bax. Furthermore, it was shown that staurosporine promoted the nuclear translocation of apoptosis-inducing factor and endonuclease G in HeLa cells. The nuclease activity associated with endonuclease G was also enhanced in response to staurosporine. However, both staurosporine-induced nuclear translocation of apoptosis-inducing factor and endonuclease G and the nuclease activity associated with endonuclease G were markedly reduced in Hela(siMst3). These results suggest that Mst3 may respond to staurosporine to trigger the caspase-independent apoptotic pathway by regulating the nuclear translocation of apoptosis-inducing factor and endonuclease G, and the nuclease activity associated with endonuclease G.
Lin
Chia-Ying
CY
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan, ROC.
Wu
Hung-Yi
HY
Wang
Pei-Ling
PL
Yuan
Chiun-Jye
CJ
D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology; D053938:DNA Fragmentation / Q000187:drug effects; D003851:Deoxyribonucleases / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D000099317:Hippo Kinases
D051033:Apoptosis Inducing Factor; D020169:Caspases; D003851:Deoxyribonucleases; D004706:Endodeoxyribonucleases; D017346:Protein Serine-Threonine Kinases; D019311:Staurosporine; C109163:STK24 protein, human; D000099317:Hippo Kinases; C052391:endonuclease G