title: CPP32 activation during dolichyl phosphate-induced apoptosis in U937 leukemia cells.
abstract: 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.
authors.affiliation: Advanced Research Center for Science and Engineering, Waseda University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: T
authors.initials: T
authors.lastname: Okubo
authors.forename: S
authors.initials: S
authors.lastname: Ozawa
authors.forename: F
authors.initials: F
authors.lastname: Nagai
authors.forename: K
authors.initials: K
authors.lastname: Ushiyama
authors.forename: I
authors.initials: I
authors.lastname: Kano
authors.forename: M
authors.initials: M
authors.lastname: Shioda
authors.forename: H
authors.initials: H
authors.lastname: Kubo
authors.forename: M
authors.initials: M
authors.lastname: Takemura
authors.forename: H
authors.initials: H
authors.lastname: Namiki
authors.forename: E
authors.initials: E
authors.lastname: Yasugi
authors.forename: M
authors.initials: M
authors.lastname: Oshima
authors.forename: Y
authors.initials: Y
authors.lastname: Seyama
authors.forename: K
authors.initials: K
authors.lastname: Kano
mesh_terms: 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
chemical_list: 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