Cleavage of eukaryotic translation initiation factor 4GII correlates with translation inhibition during apoptosis.
Eukaryotic translation initiation factor 4G (eIF4G), which has two homologs known as eIF4GI and eIF4GII, functions in a complex (eIF4F) which binds to the 5' cap structure of cellular mRNAs and facilitates binding of capped mRNA to 40S ribosomal subunits. Disruption of this complex in enterovirus-infected cells through eIF4G cleavage is known to block this step of translation initiation, thus leading to a drastic inhibition of cap-dependent translation. Here, we show that like eIF4GI, the newly identified homolog eIF4GII is cleaved during apoptosis in HeLa cells and can serve as a substrate for caspase 3. Proteolysis of both eIF4GI and eIF4GII occurs with similar kinetics and coincides with the profound translation inhibition observed in cisplatin-treated HeLa cells. Both eIF4GI and eIF4GII can be cleaved by caspase 3 with similar efficiency in vitro, however, eIF4GII is processed into additional fragments which destroy its core central domain and likely contributes to the shutoff of translation observed in apoptosis. Cell Death and Differentiation (2000) 7, 1234 - 1243.
Marissen
W E
WE
Department of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, OK 73104, USA.
Gradi
A
A
Sonenberg
N
N
Lloyd
R E
RE
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D039603:Eukaryotic Initiation Factor-4G; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; C113920:EIF4G1 protein, human; C491300:EIF4G2 protein, human; D039603:Eukaryotic Initiation Factor-4G; D010446:Peptide Fragments; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002945:Cisplatin