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Cleavage of eIF4G by HIV‐1 protease: effects on translation
Author(s) -
Perales Celia,
Carrasco Luis,
Ventoso Iván
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03764-x
Subject(s) - eif4g , cleavage (geology) , protease , chemistry , eukaryotic translation , internal ribosome entry site , microbiology and biotechnology , translation (biology) , biology , virology , messenger rna , biochemistry , enzyme , gene , paleontology , fracture (geology)
We have recently reported that HIV‐1 protease (PR) cleaves the initiation factor of translation eIF4GI [Ventoso et al., Proc. Natl. Acad. Sci. USA 98 (2001) 12966–12971]. Here, we analyze the proteolytic activity of HIV‐1 PR on eIF4GI and eIF4GII and its implications for the translation of mRNAs. HIV‐1 PR efficiently cleaves eIF4GI, but not eIF4GII, in cell‐free systems as well as in transfected mammalian cells. This specific proteolytic activity of the retroviral protease on eIF4GI was more selective than that observed with poliovirus 2A pro . Despite the presence of an intact endogenous eIF4GII, cleavage of eIF4GI by HIV‐1 PR was sufficient to impair drastically the translation of capped and uncapped mRNAs. In contrast, poliovirus IRES‐driven translation was unaffected or even enhanced by HIV‐1 PR after cleavage of eIF4GI. Further support for these in vitro results has been provided by the expression of HIV‐1 PR in COS cells from a Gag‐PR precursor. Our present findings suggest that eIF4GI intactness is necessary to maintain cap‐dependent translation, not only in cell‐free systems but also in mammalian cells.