Cleavage of eukaryotic translation initiation factor 4GII correlates with translation inhibition during apoptosis

被引:65
作者
Marissen, WE
Gradi, A
Sonenberg, N
Lloyd, RE [1 ]
机构
[1] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA
[2] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA
[3] McGill Univ, Dept Biochem, Montreal, PQ, Canada
[4] McGill Univ, McGill Canc Ctr, Montreal, PQ, Canada
关键词
translation initiation factor; elF4G; caspase; apoptosis; protein synthesis inhibition;
D O I
10.1038/sj.cdd.4400750
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1234 / 1243
页数:10
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