Proteasomes and RARS modulate AIMP1/EMAP II secretion in human cancer cell lines.
The aminoacyl t-RNA synthetase interacting multifunctional protein (AIMP1) is the precursor of the multifunctional inflammatory cytokine endothelial monocyte-activating polypeptide II (EMAP II). We previously demonstrated that AIMP1 secretion by pituitary adenomas is inversely correlated with tumor diameter and with RARS expression, suggesting that a high amount of RARS associated with AIMP1 might prevent the secretion of the latter cytokine. In this study, we investigated the role of RARS in modulating the secretion of AIMP1 in HeLa and MCF7 cell lines and investigated the possible role of the multicatalytic protease in the cleavage of AIMP1 to generate EMAP II. Our data show that RARS over-expression impairs AIMP1 secretion by both HeLa and MCF7 cells. Moreover, proteasome inhibition impairs AIMP1 cleavage to produce EMAP II. These data indicate that RARS over-expression associates with a reduced AIMP1 secretion and that the multicatalytic protease is involved in the generation of the mature cytokine, EMAP II.
Bottoni
Arianna
A
Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Ferrara, Italy.
Vignali
Cristina
C
Piccin
Daniela
D
Tagliati
Federico
F
Luchin
Andrea
A
Zatelli
Maria Chiara
MC
Uberti
Ettore C Degli
EC
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D001126:Arginine-tRNA Ligase / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
D015853:Cysteine Proteinase Inhibitors; D016207:Cytokines; D009363:Neoplasm Proteins; D061988:Proteasome Inhibitors; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1; C067713:lactacystin; D046988:Proteasome Endopeptidase Complex; D001126:Arginine-tRNA Ligase; D000111:Acetylcysteine