Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.16 (HIV-1 protease)
 2,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In eukaryotic cells, protein synthesis is regulated by a set of initiation factors (eIF) that are required for recruiting the 40 S ribosomal subunit onto the mRNA molecule. Among these proteins, eIF4GI, which is targeted by picornaviral proteases, makes a bridge between the mRNA cap structure (via eIF4E) and the 40 S ribosome (via eIF3). Recently, internal ribosome entry segment (IRES) elements have been characterized in the genomic RNA of both simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1), suggesting that viral expression of these two viruses can be regulated at the translational level. Thus, by analogy with members of the picornavirus family, we have investigated the action of the HIV-1 protease on initiation factors eIF4GI and eIF4GII using cell extracts and the rabbit reticulocyte lysate system. Our results show that eIF4GI, but not eIF4GII, is substrate for HIV-1 protease and this effect can be prevented by a HIV-1 protease inhibitor, palinavir. However, in contrast to picornaviral proteases, the cleavage of eIF4GI by HIV-1 protease occurs at multiple sites and impairs translation of both cap-dependent and IRES-containing RNAs, except for the HCV IRES, which does not require eIF4GI or eIF4GII for activity.
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PMID:In vitro cleavage of eIF4GI but not eIF4GII by HIV-1 protease and its effects on translation in the rabbit reticulocyte lysate system. 1205 64

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.
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PMID:Cleavage of eIF4G by HIV-1 protease: effects on translation. 1250 64