The EMAPII Cytokine Is Released from the Mammalian Multisynthetase Complex after Cleavage of Its p43/proEMAPII Component

Vyacheslav Shalak, Monika Kaminska, Rita Mitnacht-Kraus, Peter Vandenabeele, Matthias Clauss, Marc Mirande

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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 of in 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/proEMA-PII 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.

Original languageEnglish (US)
Pages (from-to)23769-23776
Number of pages8
JournalJournal of Biological Chemistry
Issue number26
StatePublished - Jun 29 2001


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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