V. Shalak et al., The EMAPII cytokine is released from the mammalian multisynthetase complexafter cleavage of its p43/proEMAPII component, J BIOL CHEM, 276(26), 2001, pp. 23769-23776
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.