GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

TableEdit

Jump to: navigation, search

PMID:16611992

You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki

See Help for Help on this wiki. See the documentation for how to use the table editor

Citation

Zheng, L, Bidere, N, Staudt, D, Cubre, A, Orenstein, J, Chan, FK and Lenardo, M (2006) Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1. Mol. Cell. Biol. 26:3505-13

Abstract

Stimulation of tumor necrosis factor receptor 1 (TNFR1) can initiate several cellular responses, including apoptosis, which relies on caspases, necrotic cell death, which depends on receptor-interacting protein kinase 1 (RIP1), and NF-kappaB activation, which induces survival and inflammatory responses. The TNFR-associated death domain (TRADD) protein has been suggested to be a crucial signal adaptor that mediates all intracellular responses from TNFR1. However, cells with a genetic deficiency of TRADD are unavailable, precluding analysis with mature immune cell types. We circumvented this problem by silencing TRADD expression with small interfering RNA. We found that TRADD is required for TNFR1 to induce NF-kappaB activation and caspase-8-dependent apoptosis but is dispensable for TNFR1-initiated, RIP1-dependent necrosis. Our data also show that TRADD and RIP1 compete for recruitment to the TNFR1 signaling complex and the distinct programs of cell death. Thus, TNFR1-initiated intracellular signals diverge at a very proximal level by the independent association of two death domain-containing proteins, RIP1 and TRADD. These single transducers determine cell fate by triggering NF-kappaB activation, apoptosis, and nonapoptotic death signals through separate and competing signaling pathways.

Links

PubMed PMC1447428 Online version:10.1128/MCB.26.9.3505-3513.2006

Keywords

Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/physiology; Apoptosis/genetics; Caspase 8; Caspases/genetics; Caspases/physiology; Fas-Associated Death Domain Protein; Humans; Jurkat Cells; NF-kappa B/metabolism; Nuclear Pore Complex Proteins/genetics; Nuclear Pore Complex Proteins/metabolism; Nuclear Pore Complex Proteins/physiology; RNA Interference; RNA, Small Interfering/genetics; RNA, Small Interfering/pharmacology; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism; RNA-Binding Proteins/physiology; Receptors, Tumor Necrosis Factor, Type I/agonists; Receptors, Tumor Necrosis Factor, Type I/metabolism; TNF Receptor-Associated Factor 2/metabolism; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/genetics; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/physiology; Tumor Necrosis Factor-alpha/pharmacology

public



Cancel