The EMAPII cytokine is released from the mammalian multisynthetase complex after cleavage of its p43/proEMAPII component.
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 (K(D) = 0.2 microm) as compared with its isolated N or C domains (7.5 microm and 40 microm, 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.
Shalak
V
V
Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, 1 Avenue de la Terrasse, 91190 Gif-sur-Yvette, France.
Kaminska
M
M
Mitnacht-Kraus
R
R
Vandenabeele
P
P
Clauss
M
M
Mirande
M
M
D000818:Animals; D001665:Binding Sites; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D009000:Monocytes / Q000276:immunology; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012343:RNA, Transfer / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*
D016207:Cytokines; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D011498:Protein Precursors; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1; D012343:RNA, Transfer; C505520:CASP7 protein, human; C505524:Casp7 protein, mouse; D053179:Caspase 7; D020169:Caspases