scholarly journals The Src Homology 3 Domain-containing Guanine Nucleotide Exchange Factor Is Overexpressed in High-grade Gliomas and Promotes Tumor Necrosis Factor-like Weak Inducer of Apoptosis-Fibroblast Growth Factor-inducible 14-induced Cell Migration and Invasion via Tumor Necrosis Factor Receptor-associated Factor 2

2013 ◽  
Vol 288 (30) ◽  
pp. 21887-21897 ◽  
Author(s):  
Shannon P. Fortin Ensign ◽  
Ian T. Mathews ◽  
Jennifer M. Eschbacher ◽  
Joseph C. Loftus ◽  
Marc H. Symons ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Migration And Invasion ◽  
Nucleotide Exchange ◽  
Src Homology 3 ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Src Homology ◽  
Necrosis Factor

scholarly journals Tumor Necrosis Factor Receptor 1 Is an ATPase Regulated by Silencer of Death Domain

2002 ◽  
Vol 22 (8) ◽  
pp. 2536-2543 ◽  
Author(s):  
Kiyoshi Miki ◽  
Edward M. Eddy
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Atp Binding ◽  
Death Domain ◽  
Nucleotide Exchange ◽  
Phosphate Binding ◽  
Self Aggregation ◽  
Necrosis Factor

ABSTRACT Self-aggregation of tumor necrosis factor receptor type 1 (TNFR1) induces spontaneous downstream signaling and results in cell death. It has been suggested that silencer of death domain (SODD) binds TNFR1 monomers to prevent self-aggregation. We found that SODD binds through its BAG domain to the ATPase domain of Hsp70. We also determined that SODD binds through its BAG domain to TNFR1. ATP, but not nonhydrolyzable ATP-γS, regulates the SODD binding by Hsp70 or TNFR1. ATP binding by TNFR1 was abolished when a point mutation was introduced into a phosphate-binding loop motif characteristic of ATP-binding proteins, suggesting that TNFR1 functions as an ATPase. Furthermore, TNFR1 was present in aggregates in ATP-depleted cells and SODD disassembled aggregates in vitro only in the presence of ATP. These data suggest that SODD functions as a cofactor analogous to the nucleotide exchange factor BAG-1, which modulates the ATPase cycle of Hsp70 proteins. We propose a new model in which a nucleotide-dependent conformational change in TNFR1 has a key role in regulating TNF signaling.

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