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The EMAPII cytokine is released from the mammalian multisynthetase complex after cleavage of its p43/proEMAPII

V Shalak1, M Kaminska, R Mitnacht-Kraus

  • 1Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, 1 Avenue de la Terrasse, 91190 Gif-sur-Yvette, France.

The Journal of Biological Chemistry
|April 18, 2001
PubMed

Insights

The inflammatory cytokine Endothelial-monocyte-activating polypeptide II (EMAPII) is released from its precursor p43 during apoptosis. This process attracts phagocytes to engulf apoptotic cells, initiating cell death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Endothelial-monocyte-activating polypeptide II (EMAPII) is an inflammatory cytokine associated with apoptosis.
  • The precursor of EMAPII, proEMAPII, is identical to the p43 auxiliary component of the aminoacyl-tRNA synthetase complex.
  • Apoptotic conditions trigger the release of EMAPII.

Purpose of the Study:

  • To investigate the release mechanism of EMAPII from its precursor p43.
  • To determine the functional role of released EMAPII in cellular processes.
  • To elucidate the impact of p43 cleavage on tRNA binding and translation.

Main Methods:

  • In vitro digestion of p43 using caspase 7.
  • Analysis of the N-terminus of processed EMAPII.
  • Measurement of tRNA binding affinity (K(D)) for p43/proEMAPII and its isolated domains.
  • Assay for induction of human mononuclear phagocyte migration.

Main Results:

  • EMAPII domain is readily released from p43 by caspase 7 digestion.
  • In vitro-processed EMAPII induces human mononuclear phagocyte migration.
  • p43/proEMAPII exhibits strong tRNA binding (K(D) = 0.2 µM), significantly higher than its isolated domains.
  • Cleavage of p43 and release of EMAPII domain leads to loss of potent RNA binding capacity.

Conclusions:

  • Cleavage of p43 during apoptosis limits tRNA availability for aminoacyl-tRNA synthetases, potentially causing translation arrest.
  • Released EMAPII acts as a cytokine attracting phagocytes for apoptotic cell engulfment.
  • p43 functions as a molecular fuse, initiating the cell growth/cell death transition under apoptotic conditions.

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