The EMAPII cytokine is released from the mammalian multisynthetase complexafter cleavage of its p43/proEMAPII component

Endothelial-monocyte-activating polypeptide II (EMAPII) is an inflammatory cytokine released under apoptotic conditions. Its proEMAPII precursor prove d to be identical to the auxiliary p43 component of the aminoacyl-tRNA synt hetase complex. We show here that the EMAPII domain of p43 is released read ily from the complex after in vitro digestion with caspase 7 and is able to induce migration of human mononuclear phagocytes. The N terminus of in vit ro processed EMAPII coincides exactly with that of the mature cytokine isol ated from conditioned medium of fibrosarcoma cells. We also show that p43/p roEMAPII has a strong tRNA binding capacity (K-D = 0.2 muM) as compared wit h its isolated N or C domains (7.5 muM and 40 muM, respectively). The poten t general RNA binding capacity ascribed to p43/proEMAPII is lost upon the r elease of the EMAPII domain. This suggests that after onset of apoptosis, t he first consequence of the cleavage of p43 is to limit the availability of tRNA for aminoacyl-tRNA synthetases associated within the complex. Transla tion arrest is accompanied by the release of the EMAPII cytokine that plays a role in the engulfment of apoptotic cells by attracting phagocytes. As a consequence, p43 compares well with a molecular fuse that triggers the irr eversible cell growth/ cell death transition induced under apoptotic condit ions.