CPP32 activation during dolichyl phosphate-induced apoptosis in U937 leukemia cells.
Treatment of U937 cells with dolichyl phosphate led to an increase in the activity of the ICE family protease CPP32, accompanied with cleavage of pre-CPP32 to generate p17. Peptide inhibitors YVAD-cmk and Z-Asp-CH2-DCB (specific to ICE) and DEVD-CHO (specific to CPP32) blocked the dolichyl phosphate-induced apoptosis. The dolichyl phosphate-induced increase of CPP32 activity was inhibited by adenylate cyclase inhibitors, SQ 22536 and 2',5'-dideoxyadenosine. Dolichyl phosphate caused a transient increase of intracellular cAMP concentration. The results suggest that modulation of cAMP synthesis due to the stimulation of adenylate cyclase by dolichyl phosphate plays a critical role in CPP32 activation and apoptosis.
Yokoyama
Y
Y
Advanced Research Center for Science and Engineering, Waseda University, Shinjuku-ku, Tokyo, Japan.
Okubo
T
T
Ozawa
S
S
Nagai
F
F
Ushiyama
K
K
Kano
I
I
Shioda
M
M
Kubo
H
H
Takemura
M
M
Namiki
H
H
Yasugi
E
E
Oshima
M
M
Seyama
Y
Y
Kano
K
K
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases; D000242:Cyclic AMP / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D053938:DNA Fragmentation; D016048:Dideoxyadenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004288:Dolichol Phosphates / Q000494:pharmacology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007948:Leukemia, Monocytic, Acute / Q000201:enzymology*; D014407:Tumor Cells, Cultured
D000067956:Adenylyl Cyclase Inhibitors; D004288:Dolichol Phosphates; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; C028306:dolichol monophosphate; C017759:9-(tetrahydro-2-furyl)-adenine; D016048:Dideoxyadenosine; C021008:2',5'-dideoxyadenosine; D000242:Cyclic AMP; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D000262:Adenylyl Cyclases; D000225:Adenine