Proteasomes and RARS modulate AIMP1/EMAP II secretion in human cancer cell lines

The aminoacyl t-RNA synthetase interacting multifunctional protein (AIMPI) is the precursor of the multifunctional inflammatory cytokine endothelial monocyte-activating polypepticle II (EMAP II). We previously demonstrated that AIMPI secretion by pituitary adenomas is inversely correlated with tumor diameter and with RARS expression, suggesting that a high amount of RARS associated with AIMPI might prevent the secretion of the latter cytokine. In this study, we investigated the role of RARS in modulating the secretion of AIMPI in HeLa and MCF7 cell lines and investigated the possible role of the multicatalytic protease in the cleavage of AIMPI to generate EMAP II. Our data show that RARS over-expression impairs AIMPI secretion by both HeLa and MCF7 cells. Moreover, proteasome inhibition impairs AIMPI cleavage to produce EMAP II. These data indicate that RARS over-expression associates with a reduced AIMPI secretion and that the multicatalytic protease is involved in the generation of the mature cytokine, EMAP II.