Caspase-3 is necessary and sufficient for cleavage of protein synthesis eukaryotic initiation factor 4G during apoptosis.
Induction of apoptosis BJAB cells is accompanied by the rapid cleavage of protein synthesis eukaryotic initiation factor 4G and the appearance of a fragment of approximately 76 kDa. Inhibition of apoptotic proteases (caspases) has previously been shown to prevent the cleavage of eukaryotic initiation factor 4G. In MCF-7 breast carcinoma cells, which are deficient in caspase-3, eukaryotic initiation factor 4G is not cleaved but in vivo expression of caspase-3 restores eukaryotic initiation factor 4G cleavage following induction of apoptosis. Recombinant caspase-3 can also cleave eukaryotic initiation factor 4G to yield the 76 kDa fragment both in cell extracts and when the eukaryotic initiation factor 4G is presented in a purified eukaryotic initiation factor 4F complex. These results indicate that caspase-3 activity is necessary and sufficient for eukaryotic initiation factor 4G degradation.
Bushell
M
M
Biochemistry Group, School of Biological Sciences, University of Sussex, Brighton, UK.
McKendrick
L
L
Jänicke
R U
RU
Clemens
M J
MJ
Morley
S J
SJ
D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D039603:Eukaryotic Initiation Factor-4G; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D039603:Eukaryotic Initiation Factor-4G; D010448:Peptide Initiation Factors; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases