共 27 条
Restoration of NF-κB activation by tumor necrosis factor alpha receptor complex-targeted MEKK3 in receptor-interacting protein-deficient cells
被引:37
作者:

Blonska, M
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h-index: 0
机构: SUNY Buffalo, Dept Microbiol & Immunol, Sch Med & Biomed Sci, Buffalo, NY 14214 USA

You, Y
论文数: 0 引用数: 0
h-index: 0
机构: SUNY Buffalo, Dept Microbiol & Immunol, Sch Med & Biomed Sci, Buffalo, NY 14214 USA

Geleziunas, R
论文数: 0 引用数: 0
h-index: 0
机构: SUNY Buffalo, Dept Microbiol & Immunol, Sch Med & Biomed Sci, Buffalo, NY 14214 USA

Lin, X
论文数: 0 引用数: 0
h-index: 0
机构: SUNY Buffalo, Dept Microbiol & Immunol, Sch Med & Biomed Sci, Buffalo, NY 14214 USA
机构:
[1] SUNY Buffalo, Dept Microbiol & Immunol, Sch Med & Biomed Sci, Buffalo, NY 14214 USA
[2] Merck Res Labs, W Point, PA USA
关键词:
D O I:
10.1128/MCB.24.24.10757-10765.2004
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Receptor-interacting protein (RIP) plays a critical role in tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB activation. However, the mechanism by which RIP mediates TNF-alpha-induced signal transduction is not fully understood. In this study, we reconstituted RIP-deficient Jurkat T cells with a fusion protein composed of full-length MEKK3 and the death domain of RIP (MEKK3-DD). In these cells, MEKK3-DD substitutes for RIP and directly associates with TRADD in TNF receptor complexes following TNF-alpha stimulation. We found that TNF-alpha-induced NF-kappaB activation was fully restored by MEKK3-DD in these cells. In contrast, expression of a fusion protein composed of NEMO, a component of the IkappaB kinase complex, and the death domain of RIP (NEMO-DD) cannot restore TNF-alpha-induced NF-kappaB activation in RIP-deficient cells. These results indicate that the role of RIP is to specifically recruit MEKK3 to the TNF-alpha receptor complex, whereas the forced recruitment of NEMO to the TNF-alpha receptor complex is insufficient for TNF-alpha-induced NF-kappaB activation. Although MEKK2 has a high degree of homology with MEKK3, MEKK2-DD, unlike MEKK3-DD, also fails to restore TNF-alpha-induced NF-kappaB activation in RIP-deficient cells, indicating that RIP-dependent recruitment of MEKK3 plays a specific role in TNF-alpha signaling.
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页码:10757 / 10765
页数:9
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