Cleavage of eIF4G by HIV‐1 protease: effects on translation

FEBS Letters

Ventoso, Iván¹  Carrasco, Luis²  Perales, Celia² 

[1] Departamento de Biologı́a Molecular y Celular, Centro Nacional de Biotecnologı́a (CNB-CSIC), Universidad Autónoma, Cantoblanco 28049, Madrid, Spain;Centro de Biologı́a Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma-CSIC, Cantoblanco 28049, Madrid, Spain

关键词: HIV-1 protease;    eIF4GI;    eIF4GII;    Regulation of translation;    Viral protease;    Translation initiation factor;   

DOI  :  10.1016/S0014-5793(02)03764-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown