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

Jin Woo Choi1, Dae Gyu Kim, Min Chul Park

  • 1Center for Medicinal Protein Network and Systems Biology, Department of Molecular Medicine, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.

Journal of Cell Science
|July 9, 2009
PubMed

Insights

Aminoacyl-tRNA synthetase interacting multifunctional protein 2 (AIMP2) enhances TNFalpha-induced cell death by degrading TRAF2. This study elucidates AIMP2's mechanism in regulating apoptosis and TNFalpha signaling pathways.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • AIMP2 (aminoacyl-tRNA synthetase interacting multifunctional protein 2), also known as JTV-1, is involved in regulating cell proliferation and death.
  • Previous studies indicated AIMP2 augments TNFalpha-induced cell death, but its mechanism remained unclear.

Purpose of the Study:

  • To investigate the functional significance and mechanism of AIMP2 in TNFalpha signaling.
  • To elucidate how AIMP2 mediates TNFalpha-induced apoptosis.

Main Methods:

  • Utilized AIMP2-deficient or suppressed cells to assess TNFalpha-induced cell death.
  • Investigated the interaction of AIMP2 with TRAF2 and its role in the TNFalpha signaling pathway.
  • Analyzed the effect of AIMP2 on IkappaB and NFkappaB levels.
  • Examined the ubiquitylation and degradation of TRAF2 mediated by AIMP2 and c-IAP1.

Main Results:

  • TNFalpha-induced cell death was reduced in cells lacking or with suppressed AIMP2.
  • Exogenous AIMP2 enhanced sensitivity to TNFalpha signaling, increasing IkappaB and suppressing NFkappaB.
  • AIMP2 binds to TRAF2 and promotes its degradation through the ubiquitin-proteasome system via c-IAP1.
  • AIMP2 facilitates the association of c-IAP1 with TRAF2, leading to TRAF2 ubiquitination and degradation.

Conclusions:

  • AIMP2 plays a crucial role in mediating the pro-apoptotic activity of TNFalpha.
  • AIMP2 downregulates TRAF2 expression, thereby sensitizing cells to TNFalpha-induced apoptosis.
  • The findings reveal a novel mechanism by which AIMP2 regulates TNFalpha signaling and cell death.

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