cIAP-1, but not XIAP, is cleaved by caspases during the apoptosis induced by TGF-beta in fetal rat hepatocytes.
We have studied the expression of XIAP, cIAP-1 and cIAP-2 in fetal rat hepatocytes and its possible regulation by pro-apoptotic stimuli (transforming growth factor-beta (TGF-beta)) and survival signals (epidermal growth factor (EGF)). The three forms of inhibitor of apoptosis proteins (IAPs) are expressed in fetal hepatocytes and only cIAP-1, but not XIAP or cIAP-2, is cleaved during TGF-beta-induced apoptosis. The pan-caspase inhibitor Z-VAD.fmk blocked this effect, which indicates that cIAP-1 is a caspase substrate. EGF plays a dual role in the regulation of IAPs expression. On one hand, it increases cIAP-1 and cIAP-2 basal expression and, on the other hand, it blocks the cleavage of cIAP-1 by caspases induced by TGF-beta.
Herrera
Blanca
B
Departamento de Bioquímica y Biología Molecular, Centro Mixto CSIC/UCM, Facultad de Farmacia, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain.
Fernández
Margarita
M
Benito
Manuel
M
Fabregat
Isabel
I
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D051636:X-Linked Inhibitor of Apoptosis Protein
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D011506:Proteins; D016212:Transforming Growth Factor beta; D051636:X-Linked Inhibitor of Apoptosis Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D004247:DNA; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases