The p220 component of eukaryotic initiation factor 4F is a substrate for multiple calcium-dependent enzymes.
Eukaryotic initiation factor 4F (eIF-4F) is a multisubunit protein that functions in the first step of the binding of capped mRNAs to the small ribosomal subunit. Its largest polypeptide component, p220, is cleaved following poliovirus infection. This is thought to inactivate eIF-4F function, thereby preventing cap-dependent initiation of translation of cellular mRNAs. In this report, we show that p220 in extracts of uninfected HeLa cells is specifically lost in the presence of calcium. The responsible activities have been partially purified and identified as the calcium-dependent, neutral, cysteine proteases calpains I and II. In addition, a third calcium-dependent activity was resolved from the calpains and also results in the loss of p220. This activity has properties similar to a transglutaminase and copurifies with tissue transglutaminase through several chromatographic steps. None of these calcium-dependent activities appears to mediate p220 cleavage in poliovirus-infected cells.
Wyckoff
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Department of Biochemistry, University of Utah School of Medicine, Salt Lake City 84132.
Croall
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Ehrenfeld
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D002118:Calcium / Q000494:pharmacology*; D002154:Calpain / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D039562:Eukaryotic Initiation Factor-4F; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000378:metabolism*; D017955:Poliovirus / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism
D039562:Eukaryotic Initiation Factor-4F; D010446:Peptide Fragments; D010448:Peptide Initiation Factors; D014764:Viral Proteins; D011503:Transglutaminases; D002154:Calpain; D003546:Cysteine Endopeptidases; C057400:picornain 2A, Picornavirus; D002118:Calcium