Deregulation of Cdc2 kinase induces caspase-3 activation and apoptosis.
Progression of the cell cycle and control of apoptosis are tightly linked processes. It has been reported that manifestation of apoptosis requires cdc2 kinase activity yet the mechanism(s) of which is largely unclear. In an attempt to study the role of human MDM2 (HDM2) in interphase and mitosis, we employed the Xenopus cell-free system to study HDM2 protein stability. Interestingly, HDM2 is specifically cleaved in Xenopus mitotic extracts but not in the interphase extracts. We demonstrate that HDM2 cleavage is dependent on caspase-3 and that activation of cdc2 kinase results in caspase-3 activation in the Xenopus cell-free system. Furthermore, expression of cdc2 kinase in mammalian cells leads to activation of caspase-3 and apoptosis. Taken together, these data indicate that deregulation of cdc2 kinase activity can trigger apoptotic machinery that leads to caspase-3 activation and apoptosis.
Gu
Ling
L
Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
Zheng
Hongwu
H
Murray
Stephen A
SA
Ying
Haoqiang
H
Jim Xiao
Zhi-Xiong
ZX
D000818:Animals; D017209:Apoptosis; D016203:CDC2 Protein Kinase / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002457:Cell Extracts; D019926:Cyclin B / Q000096:biosynthesis; D056744:Cyclin B1; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D007399:Interphase / Q000502:physiology; D008938:Mitosis / Q000502:physiology; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D014981:Xenopus / Q000378:metabolism; D029867:Xenopus Proteins
C534699:CCNB1 protein, human; D002457:Cell Extracts; D019926:Cyclin B; D056744:Cyclin B1; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D029867:Xenopus Proteins; C497210:MDM2 protein, Xenopus; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D016203:CDC2 Protein Kinase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases