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AIMP2 promotes TNFalpha-dependent apoptosis via ubiquitin-mediated degradation of TRAF2.

Journal of cell science (2009-07-09)
Jin Woo Choi, Dae Gyu Kim, Min Chul Park, Jung Yeon Um, Jung Min Han, Sang Gyu Park, Eung-Chil Choi, Sunghoon Kim
ABSTRACT

AIMP2 (aminoacyl-tRNA synthetase interacting multifunctional protein 2; also known as JTV-1) was first identified as p38 in a macromolecular protein complex that consisted of nine different aminoacyl-tRNA synthetases and two other auxiliary factors. AIMP2 also plays pivotal roles in the regulation of cell proliferation and death. Although AIMP2 was previously shown to augment TNFalpha-induced cell death, its working mechanism in this signal pathway was not understood. Here, we investigate the functional significance and mode of action of AIMP2 in TNFalpha signaling. TNFalpha-induced cell death was compromised in AIMP2-deficient or -suppressed cells and exogenous supplementation of AIMP2 augmented apoptotic sensitivity to TNFalpha signaling. This activity was confirmed by the AIMP2-dependent increase of IkappaB and suppression of NFkappaB. We found binding of AIMP2 to TRAF2, a key player in the TNFalpha signaling pathway. AIMP2 augmented the association of an E3 ubiquitin ligase, c-IAP1, with TRAF2, causing ubiquitin-dependent degradation of TRAF2. These findings suggest that AIMP2 can mediate the pro-apoptotic activity of TNFalpha via the downregulation of TRAF2 expression.