AIMP2 promotes TNF alpha-dependent apoptosis via ubiquitin-mediated degradation of TRAF2

作者：Choi Jin Woo; Kim Dae Gyu; Park Min Chul; Um Jung Yeon; Han Jung Min; Park Sang Gyu; Choi Eung Chil; Kim Sunghoon^*

来源：Journal of Cell Science, 2009, 122(15): 2710-2715.

DOI：10.1242/jcs.049767

• AIMP2 (p38, JTV-1)
• Aminoacyl-tRNA synthetase
• TNF alpha signaling

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 TNF alpha-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 TNF alpha signaling. TNF alpha-induced cell death was compromised in AIMP2-deficient or -suppressed cells and exogenous supplementation of AIMP2 augmented apoptotic sensitivity to TNF alpha signaling. This activity was confirmed by the AIMP2-dependent increase of I kappa B and suppression of NF kappa B. We found binding of AIMP2 to TRAF2, a key player in the TNF alpha 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 TNF alpha via the downregulation of TRAF2 expression.

• 出版日期2009-8