Premature p34cdc2 activation required for apoptosis.
Activation of the serine-threonine kinase p34cdc2 at an inappropriate time during the cell cycle leads to cell death that resembles apoptosis. Premature activation of p34cdc2 was shown to be required for apoptosis induced by a lymphocyte granule protease. The kinase was rapidly activated and tyrosine dephosphorylated at the initiation of apoptosis. DNA fragmentation and nuclear collapse could be prevented by blocking p34cdc2 activity with excess peptide substrate, or by inactivating p34cdc2 in a temperature-sensitive mutant. Premature p34cdc2 activation may be a general mechanism by which cells induced to undergo apoptosis initiate the disruption of the nucleus.
Shi
L
L
Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.
Nishioka
W K
WK
Th'ng
J
J
Bradbury
E M
EM
Litchfield
D W
DW
Greenberg
A H
AH
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D004249:DNA Damage; D003851:Deoxyribonucleases / Q000494:pharmacology; D004789:Enzyme Activation; D004790:Enzyme Induction; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008938:Mitosis; D008969:Molecular Sequence Data; D054353:Perforin; D010766:Phosphorylation; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D016203:CDC2 Protein Kinase; D003851:Deoxyribonucleases; D012697:Serine Endopeptidases; C072501:fragmentin