| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3346044 | Current Opinion in Immunology | 2011 | 7 Pages |
In the past 2 years there has been an explosion of information regarding molecules that regulate TNF-R1 signalling, and even reviews published in 2010 are out of date. TNF-R1 activation of NF-κB is a text book example of a signal transduction pathway regulated by ubiquitin and many of the concepts concerning the different roles of ubiquitin chains were first outlined in TNF-R1 signalling. What was once a very simple pathway with clearly defined roles for ubiquitin in regulating TNF-R1 signalling has, however, now become so complicated that we have ‘an embarrassment of riches’ [1]. The less polite might claim our pathways of TNF-R1 signalling look as complicated as a web constructed by a drug-addled spider [2]. This review will pick apart only one small strand of the web, and will address the role of ubiquitin in the activation of NF-κB by TNF with a focus on interpreting in vivo results. Nevertheless some of the concepts, for example the role of linear ubiquitin chains in regulating signalling, may be applicable to the family in general.
► This review focuses on ubiquitin and the role of E3 enzymes that attach it to substrates in regulating TNF signalling. ► This review highlights the results from mice that have components of the TNF signalling complex knocked out. ► Recently described types of ubiquitin modification in TNF signalling such as K11- and linear ubiquitin chains are discussed. ► New models of TNF signalling based on recent research and analysis in this review are proposed.
