The p43 component of the mammalian multi-synthetase complex is likely to be the precursor of the endothelial monocyte-activating polypeptide II cytokine.
p43 is one of the three auxiliary components invariably associated with nine aminoacyl-tRNA synthetases as a multienzyme complex ubiquitous to all eukaryotic cells from flies to humans. The cDNA encoding the hamster protein was isolated by using mixed oligonucleotides deduced from peptide sequences. The 359-amino acid protein is the hamster homologue of the recently reported murine and human EMAP II cytokine implicated in a variety of inflammatory disorders. The sequence of several proEMAP II proteins suggests that the p43 component of the complex is the precursor of the active mature cytokine after cleavage at a conserved Asp residue. The COOH-terminal moiety of p43 is also homologous to polypeptide domains found in bacterial methionyl- or phenylalanyl-tRNA synthetases and in the yeast Arc1p/G4p1 protein that associates with yeast methionyl-tRNA synthetase. Our results implicate the COOH-terminal moiety of p43 as a RNA binding domain. In the native state, as a component of the multisynthetase complex, p43 may be required for tRNA channeling and, after proteolytic processing occurring in tumor cells, would acquire inflammatory properties possibly related to apoptosis. The release of a truncated p43 from the complex could be involved in mediation of the signaling of tumor cells and stimulation of an acute inflammatory response.
Quevillon
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S
Laboratoire d'Enzymologie et Biochimie Structurales, CNRS-UPR 9063, 91190 Gif-sur-Yvette, France.
Agou
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F
Robinson
J C
JC
Mirande
M
M
D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002850:Chromatography, Gel; D006224:Cricetinae; D016207:Cytokines; D018076:DNA, Complementary; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D016207:Cytokines; D018076:DNA, Complementary; D009363:Neoplasm Proteins; D011498:Protein Precursors; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1; D000604:Amino Acyl-tRNA Synthetases