PROTEIN SYNTHESIS POST-TRANSLATION MODIFICATION AND DEGRADATION
The EMAPII Cytokine Is Released from the Mammalian Multisynthetase Complex after Cleavage of Its p43/proEMAPII Component*

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Endothelial-monocyte-activating polypeptide II (EMAPII) is an inflammatory cytokine released under apoptotic conditions. Its proEMAPII precursor proved to be identical to the auxiliary p43 component of the aminoacyl-tRNA synthetase complex. We show here that the EMAPII domain of p43 is released readily from the complex after in vitro digestion with caspase 7 and is able to induce migration of human mononuclear phagocytes. The N terminus ofin vitro-processed EMAPII coincides exactly with that of the mature cytokine isolated from conditioned medium of fibrosarcoma cells. We also show that p43/proEMAPII has a strong tRNA binding capacity (KD = 0.2 μm) as compared with its isolated N or C domains (7.5 μm and 40 μm, respectively). The potent general RNA binding capacity ascribed to p43/proEMAPII is lost upon the release of the EMAPII domain. This suggests that after onset of apoptosis, the first consequence of the cleavage of p43 is to limit the availability of tRNA for aminoacyl-tRNA synthetases associated within the complex. Translation 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 irreversible cell growth/cell death transition induced under apoptotic conditions.

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Published, JBC Papers in Press, April 16, 2001, DOI 10.1074/jbc.M100489200

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This work was supported in part by grants from the Program Physique et Chimie du Vivant from CNRS, the Association pour la Recherche sur le Cancer, and La Ligue. V. S. was supported by INTAS (YSF 99-208) and NATO fellowships. M. K. was supported in part by grants from the Jumelage Franco-Polonais program from CNRS.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Present address: Inst. of Bioorganic Chemistry, Polish Academy of Sciences, 60-704 Poznan, Poland.