Sequestration of TRAF2 into stress granules interrupts tumor necrosis factor signaling under stress conditions.
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.
Kim
Woo Jae
WJ
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.
Back
Sung Hoon
SH
Kim
Vit
V
Ryu
Incheol
I
Jang
Sung Key
SK
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*
D039603:Eukaryotic Initiation Factor-4G; D016328:NF-kappa B; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha
Int J Biochem Cell Biol. 1999 Jan;31(1):37-41
10216942
EMBO J. 1993 Aug;12(8):3095-104
8344250
Protein Expr Purif. 2000 Nov;20(2):196-206
11049744
Mol Cell Biol. 2000 Jan;20(2):468-77
10611225
Mol Biol Cell. 2002 Jan;13(1):195-210
11809833
J Toxicol Environ Health A. 2001 Aug 10;63(7):475-93
11497330
Oncogene. 2001 Oct 1;20(44):6482-91
11607847
Biochem Biophys Res Commun. 2002 Mar 1;291(3):453-7
11855810
Science. 1998 Sep 11;281(5383):1680-3
9733516
J Virol. 2002 Mar;76(5):2529-42
11836431
J Biol Chem. 2000 Jun 16;275(24):18022-8
10751398
Exp Cell Res. 2000 Jan 10;254(1):14-24
10623461
Exp Cell Res. 2003 Nov 1;290(2):227-33
14567982
J Cell Biol. 1999 Dec 27;147(7):1431-42
10613902
Biochem Biophys Res Commun. 2000 Jun 16;272(3):936-45
10860854
Cell Stress Chaperones. 2002 Apr;7(2):213-21
12380690
Nature. 2001 Nov 15;414(6861):313-7
11713531
N Engl J Med. 1997 Apr 10;336(15):1066-71
9091804
Mol Cell Biol. 1983 Sep;3(9):1648-55
6633535
Am J Physiol Cell Physiol. 2003 Feb;284(2):C273-84
12388085
J Biol Chem. 2001 Nov 16;276(46):42728-36
11559697
J Clin Invest. 1995 Apr;95(4):1854-60
7706492
Mol Cell Biol. 1998 Jan;18(1):334-42
9418880
J Appl Physiol (1985). 1992 Oct;73(4):1517-22
1447099
Genes Dev. 2000 Jun 15;14(12):1460-70
10859165
Mol Cell Biol. 2002 Jul;22(13):4499-511
12052860
J Cell Biochem. 2002;84(4):687-98
11835394
FASEB J. 2001 Jan;15(1):270-274
11149915
J Biol Chem. 2001 Mar 16;276(11):8341-9
11112773
Biochem Soc Trans. 2002 Nov;30(Pt 6):963-9
12440955
J Biol Chem. 1987 Oct 25;262(30):14538-43
3667588
Shock. 2000 Oct;14(4):447-50
11049108
Biochem J. 1996 Aug 15;318 ( Pt 1):187-93
8761470
Crit Care Med. 2002 Jan;30(1 Supp):S89-S95
11891409
Annu Rev Biochem. 1999;68:913-63
10872469
Mol Cell Biol. 1998 Apr;18(4):2240-51
9528795
J Exp Med. 2002 Oct 7;196(7):923-34
12370254
J Immunol. 1998 Jul 1;161(1):319-24
9647239
Biochem Biophys Res Commun. 1997 Apr 28;233(3):592-600
9168896
Immunity. 2002 May;16(5):685-95
12049720
Am J Physiol. 1993 Dec;265(6 Pt 2):R1447-57
8285289
Immunity. 2000 Mar;12(3):301-11
10755617
Mol Cell Biol. 2001 Jun;21(11):3632-41
11340157
Nature. 1999 Apr 8;398(6727):533-8
10206649
Surgery. 1995 Sep;118(3):510-6
7652687
J Cell Sci. 2002 Aug 15;115(Pt 16):3227-34
12140254
J Clin Invest. 1995 Apr;95(4):1446-56
7706448
J Cell Biol. 1989 Oct;109(4 Pt 1):1467-81
2793930
J Clin Invest. 1998 Feb 15;101(4):855-62
9466981
J Cell Biol. 2000 Dec 11;151(6):1257-68
11121440