Apoptosis induction by the binding of the carboxyl terminus of human immunodeficiency virus type 1 gp160 to calmodulin.
The role of calmodulin (CaM) in apoptosis induced by gp160 of human immunodeficiency virus type 1 was investigated with cells undergoing single-cell killing. These cells were found to express, under the control of an inducible promoter, wild-type gp160 or mutant gp160 devoid of various lengths of the carboxyl terminus. Immunoprecipitation accompanied by immunoblotting revealed binding of CaM to wild-type gp160 but not to mutant gp160 bearing a carboxyl terminus with a deletion spanning more than five amino acid residues. A significant coenzyme activity was detected in the CaM bound to gp160 even in the presence of a Ca2+ chelater, EGTA. The cells forming this gp160-CaM complex exhibited an elevated intracellular Ca2+ level followed by DNA fragmentation, which is a hallmark of apoptosis, and finally cell killing, while the cells not forming this complex did not show any significant elevation in Ca2+ level or DNA fragmentation. These results thus indicated that CaM plays a key role in gp160-induced apoptosis.
Ishikawa
H
H
Department of Infectious Diseases, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
Sasaki
M
M
Noda
S
S
Koga
Y
Y
D017209:Apoptosis; D015704:CD4 Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D015536:Down-Regulation; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D016296:Mutagenesis; D014407:Tumor Cells, Cultured
D015704:CD4 Antigens; D002147:Calmodulin; D019302:HIV Envelope Protein gp160; D002118:Calcium