title: Sequestration of TRAF2 into stress granules interrupts tumor necrosis factor signaling under stress conditions.
abstract: The cellular stress response (SR) is a phylogenetically conserved protection mechanism that involves inhibition of protein synthesis through recruitment of translation factors such as eIF4G into insoluble stress granules (SGs) and blockade of proinflammatory responses by interruption of the signaling pathway from tumor necrosis factor alpha (TNF-alpha) to nuclear factor-kappaB (NF-kappaB) activation. However, the link between these two physiological phenomena has not been clearly elucidated. Here we report that eIF4GI, which is a scaffold protein interacting with many translation factors, interacts with TRAF2, a signaling molecule that plays a key role in activation of NF-kappaB through TNF-alpha. These two proteins colocalize in SGs during cellular exposure to stress conditions. Moreover, TRAF2 is absent from TNFR1 complexes under stress conditions even after TNF-alpha treatment. This suggests that stressed cells lower their biological activities by sequestration of translation factors and TRAF2 into SGs through a protein-protein interaction.
authors.affiliation: National Research Laboratory, Postech Biotech Center, Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Hyoja-Dong San 31, Pohang, Kyungbuk 790-784, Korea.
authors.forename: Woo Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Back
authors.forename: Vit
authors.initials: V
authors.lastname: Kim
authors.forename: Incheol
authors.initials: I
authors.lastname: Ryu
authors.forename: Sung Key
authors.initials: SK
authors.lastname: Jang
mesh_terms: D002460:Cell Line; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000378:metabolism*; D039603:Eukaryotic Initiation Factor-4G / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D047992:TNF Receptor-Associated Factor 2 / Q000032:analysis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D039603:Eukaryotic Initiation Factor-4G; D016328:NF-kappa B; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha
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