Increased p34cdc2-dependent kinase activity during apoptosis: a possible activation mechanism of DNase I leading to DNA breakdown.
Cells undergoing apoptosis typically exhibit distinctive morphological characteristics. Early events include the rounding up of the cell, chromatin condensation, nuclear membrane breakdown and blebbing of the cellular membrane. Strikingly similar changes take place in the cell cycle progression, at the entry into mitosis, suggesting a link between mitosis and apoptosis. Here we show that expression of active p34cdc2 at inappropriate phases during the cell cycle leads to morphological changes reminiscent of apoptosis, including DNA degradation. Cells cotransfected with the active mutant of p34cdc2 and DNase I displayed degraded DNA, which was absent in p34cdc2 wild-type and DNase I-transfected cells, in spite of similar DNase activities. Upon induction of apoptosis in thymocytes, transient p34cdc2 activation was detected prior to lamina breakdown and nuclease activation. P34cdc2 activation was also observed during APO-1 (Fas/CD95)-induced apoptosis in a B lymphoblastoma cell line. Our results suggest that unscheduled activation of p34cdc2 may participate in the initiation of the typical apoptotic phenotype.
Schroter
M
M
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Peitsch
M C
MC
Tschopp
J
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D016923:Cell Death; D002645:Chickens; D004249:DNA Damage; D003850:Deoxyribonuclease I / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D051381:Rats; D012995:Solubility; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D014162:Transfection; D014407:Tumor Cells, Cultured
D003907:Dexamethasone; D016203:CDC2 Protein Kinase; D003850:Deoxyribonuclease I