Compartmentalization of TNF Receptor 1 SignalingInternalized TNF Receptosomes as Death Signaling Vesicles

Compartmentalization of TNF receptor 1 signaling: internalized TNF receptosomes as death signaling vesicles.

The molecular regulation of the recruitment of initial signaling complexes at the TNF-R1 is poorly defined. We demonstrate here that within minutes internalized TNF-R1 (TNF receptosomes) recruits TRADD, FADD, and caspase-8 to establish the "death-inducing signaling complex" (DISC). In addition, we identified the TNF-R1 internalization domain (TRID) required for receptor endocytosis and provide ...

Cardiac glycosides inhibit TNF- NF- B signaling by blocking recruitment of TNF receptor-associated death domain to the TNF receptor

*Department of Anatomy, Physiology, and Genetics and Institute for Molecular Medicine, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; †Cancer and Cell Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and §Protein Expression Laboratory, National Cancer Institute SAIC, Nationa...

Contenders in FasL/TNF death signaling

A variety of biological functions are regulated through extracellular signals. One of the most unexpected responses to emerge has been receptor-mediated control of programmed cell death, or apoptosis. Apoptosis is a morphologically defined process, characterized by the condensation of the nucleus and cytoplasm and a distinctive pattern of chromosomal DNA fragmentation. Extracellular regulation ...

Histamine antagonizes TNF signaling 1 Histamine antagonizes TNF signaling by stimulating TNF receptor shedding from the cell surface and Golgi storage pool

Selective death of autoreactive T cells in human diabetes by TNF or TNF receptor 2 agonism.

Human autoimmune (AI) diseases are difficult to treat, because immunosuppressive drugs are nonspecific, produce high levels of adverse effects, and are not based on mechanistic understanding of disease. Destroying the rare autoreactive T lymphocytes causing AI diseases would improve treatment. In animal models, TNF selectively kills autoreactive T cells, thereby hampering disease onset or progr...