title: The eukaryotic translation initiation factor 4GI is cleaved by different retroviral proteases.
abstract: The initiation factor eIF4G plays a central role in the regulation of translation. In picornaviruses, as well as in human immunodeficiency virus type 1 (HIV-1), cleavage of eIF4G by the viral protease leads to inhibition of protein synthesis directed by capped cellular mRNAs. In the present work, cleavage of both eIF4GI and eIF4GII has been analyzed by employing the proteases encoded within the genomes of several members of the family Retroviridae, e.g., Moloney murine leukemia virus (MoMLV), mouse mammary tumor virus, human T-cell leukemia virus type 1, HIV-2, and simian immunodeficiency virus. All of the retroviral proteases examined were able to cleave the initiation factor eIF4GI both in intact cells and in cell-free systems, albeit with different efficiencies. The eIF4GI hydrolysis patterns obtained with HIV-1 and HIV-2 proteases were very similar to each other but rather different from those obtained with MoMLV protease. Both eIF4GI and eIF4GII were cleaved very efficiently by the MoMLV protease. However, eIF4GII was a poor substrate for HIV proteases. Proteolytic cleavage of eIF4G led to a profound inhibition of cap-dependent translation, while protein synthesis driven by mRNAs containing internal ribosome entry site elements remained unaffected or was even stimulated in transfected cells.
authors: Centro de Biología Molecular (CSIC-UAM), Facultad de Ciencias, Universidad Autónoma, Cantoblanco, 28049 Madrid, Spain. ealvarez@cbm.uam.es
authors: Enrique
authors: E
authors: Alvarez
authors: Luis
authors: L
authors: Menéndez-Arias
authors: Luis
authors: L
authors: Carrasco
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D017931:DNA Primers; D010450:Endopeptidases / Q000378:metabolism*; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism* / Q000502:physiology; D006868:Hydrolysis; D012190:Retroviridae / Q000201:enzymology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D039603:Eukaryotic Initiation Factor-4G; D010450:Endopeptidases