Cyclin-dependent kinase-1: linking apoptosis to cell cycle and mitotic catastrophe.
The cyclin-dependent kinase 1 (Cdk1), formerly called Cdc2 (or p34(Cdc2)), interacts with cyclin B1 to form an active heterodimer. The activity of Cdk1 is subjected to a complex spatiotemporary regulation, required to guarantee its scheduled contribution to the mitotic prophase and metaphase. Moreover, the activation of Cdk1 may be required for apoptosis induction in some particular pathways of cell killing. This applies to several clinically important settings, for instance to paclitaxel-induced killing of breast cancer cells, in which the ErbB2 receptor kinase can mediate apoptosis inhibition through inactivation of Cdk1. The activation of Cdk1 participates also in HIV-1-induced apoptosis, upstream of the p53-dependent mitochondrial permeabilization step. An unscheduled Cdk1 activation may contribute to neuronal apoptosis occurring in neurodegenerative diseases. Finally, the premature activation of Cdk1 can lead to mitotic catastrophe, for instance after irradiation-induced DNA damage. Thus, a cell type-specific modulation of Cdk1 might be taken advantage of for the therapeutic correction of pathogenic imbalances in apoptosis control.
Castedo
M
M
Centre National de la Recherche Scientifique, UMR1599, Institut Gustave Roussy, 39 rue Camille-Desmoulins, F-94805 Villejuif, France.
Perfettini
J-L
JL
Roumier
T
T
Kroemer
G
G
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D008938:Mitosis / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism
D016203:CDC2 Protein Kinase