Activation of cyclin-dependent kinase 5 is a consequence of cell death.
Cyclin-dependent kinase 5 (Cdk5) is similar to other Cdks but is activated during cell differentiation and cell death rather than cell division. Since activation of Cdk5 has been reported in many situations leading to cell death, we attempted to determine if it was required for any form of cell death. We found that Cdk5 is activated during apoptotic deaths and that the activation can be detected even when the cells continue to secondary necrosis. This activation can occur in the absence of Bim, calpain, or neutral cathepsins. The kinase is typically activated by p25, derived from p35 by calpain-mediated cleavage, but inhibition of calpain does not affect cell death or the activation of Cdk5. Likewise, RNAi-forced suppression of the synthesis of Cdk5 does not affect the incidence or kinetics of cell death. We conclude that Cdk5 is activated as a consequence of metabolic changes that are common to many forms of cell death. Thus its activation suggests processes during cell death that will be interesting or important to understand, but activation of Cdk5 is not necessary for cells to die.
Ye
Yixia
Y
Department of Biology, Queens College and Graduate Center of the City University of New York, Flushing, NY 11367, USA.
Tinari
Antonella
A
Malorni
Walter
W
Lockshin
Richard A
RA
Zakeri
Zahra
Z
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D019556:COS Cells; D002154:Calpain / Q000378:metabolism; D002403:Cathepsins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002522:Chlorocebus aethiops; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D002403:Cathepsins; D002154:Calpain