20S proteasome differentially alters translation of different mRNAs via the cleavage of eIF4F and eIF3.
The molecular basis for coordinated regulation of protein synthesis and degradation is not understood. Here we report that the 20S proteasome endoproteolytically cleaves the translation initiation factors eIF4G, a subunit of eIF4F, and eIF3a, a subunit of eIF3. The cleavage of eIF4G or eIF3a differentially affects the assembly of ribosomal preinitiation complexes on different cellular and viral mRNAs in an in vitro system containing pure components. Inhibition of proteolytic activity of the 20S proteasome with specific inhibitors prevents cleavage of both factors in vitro and in vivo, restores assembly of ribosomal complexes in vitro, and differentially affects translation of different mRNAs in vivo. These studies demonstrate the importance of the endoproteolytic activity of proteasomes in regulation of cellular processes and suggest a link between protein synthesis and degradation.
Baugh
James M
JM
Committee on Microbiology, Department of Molecular Genetics and Cell Biology, University of Chicago, 920 East 58th Street, Chicago, Illinois 60637, USA.
Pilipenko
Evgeny V
EV
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D004926:Escherichia coli / Q000235:genetics; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism*; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism*; D030041:Hepatitis A virus / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism* / Q000648:ultrastructure; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
D039621:Eukaryotic Initiation Factor-3; D039562:Eukaryotic Initiation Factor-4F; D012333:RNA, Messenger; D046988:Proteasome Endopeptidase Complex