TNF and ubiquitin at the crossroads of gene activation, cell death, inflammation, and cancer

Tumor necrosis factor (TNF) is crucial for innate immunity, but deregulated TNF signaling also plays an eminent role in the pathogenesis of many chronic inflammatory diseases and cancer‐related inflammation. The signals that mediate both the beneficial and the harmful effects of TNF are initiated wh...

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Vydáno v:Immunological reviews Ročník 244; číslo 1; s. 9 - 28
Hlavní autor: Walczak, Henning
Médium: Journal Article
Jazyk:angličtina
Vydáno: Oxford, UK Blackwell Publishing Ltd 01.11.2011
Témata:
Apoptosis - genetics
Apoptosis - immunology
apoptosis/autophagy
Autophagy - genetics
Autophagy - immunology
cytokines
cytotoxicity
Humans
Immunity, Innate
Inflammation - genetics
Inflammation - immunology
Inflammation - metabolism
Neoplasms - genetics
Neoplasms - immunology
Neoplasms - metabolism
Protein Binding - genetics
Receptors, Tumor Necrosis Factor, Type I - genetics
Receptors, Tumor Necrosis Factor, Type I - immunology
Receptors, Tumor Necrosis Factor, Type I - metabolism
Receptors, Tumor Necrosis Factor, Type II - genetics
Receptors, Tumor Necrosis Factor, Type II - immunology
Receptors, Tumor Necrosis Factor, Type II - metabolism
signal transduction
Signal Transduction - genetics
Signal Transduction - immunology
signaling proteins
Transcriptional Activation - immunology
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - immunology
Tumor Necrosis Factor-alpha - metabolism
Ubiquitin - genetics
Ubiquitin - immunology
Ubiquitin - metabolism
Ubiquitination - genetics
Ubiquitination - immunology
ISSN:0105-2896, 1600-065X, 1600-065X
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Shrnutí:Tumor necrosis factor (TNF) is crucial for innate immunity, but deregulated TNF signaling also plays an eminent role in the pathogenesis of many chronic inflammatory diseases and cancer‐related inflammation. The signals that mediate both the beneficial and the harmful effects of TNF are initiated when TNF binds to its receptors on the surface of target cells. TNF receptor 1 (TNFR1) is ubiquitously expressed, whereas TNFR2 is mainly expressed on lymphocytes and endothelial cells. This review focuses on the molecular and physiological consequences of the interaction of TNF with TNFR1. The different outcomes of TNF signaling originate at the apical signaling complex that forms when TNF binds to TNFR1, the TNFR1 signaling complex (TNF‐RSC). By integrating recently gained insight on the functional importance of the presence of different types of ubiquitination in the TNF‐RSC, including linear ubiquitin linkages generated by the linear ubiquitin chain assembly complex (LUBAC), with the equally recent elucidation of the mode in which ubiquitin‐binding domains interact with specific di‐ubiquitin linkages, this review develops a new concept for the way the concerted action of different ubiquitination events enables the TNF‐RSC to generate its signaling output in a spatio‐temporally controlled manner. Finally, it will be explained how these new findings and the emerging concept of differential ubiquitination governing the TNF‐RSC may impact future research on the molecular mechanism of TNF signaling and the function of this cytokine in normal physiology, chronic inflammation, and cancer.
Bibliografie:ark:/67375/WNG-J2FXH3GW-8
istex:DD4AB6DF54AE4BFACCC5B7ECE53BE6AE4AF6D268
ArticleID:IMR1066
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
content type line 23
ISSN:0105-2896
1600-065X
1600-065X
DOI:10.1111/j.1600-065X.2011.01066.x