New Perspectives in TNF-R1-Induced NF-κB Signaling

  • Ian E. Gentle
  • John Silke
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 691)


The ubiquitylation events leading to activation of NF-κB at the TNFR1 receptor have been a topic of intense study. It is believed that K63 ubiquitylation of the kinase RIPK1 is required for recruitment of the TAB2/TAB3/TAK1 and IKK1/IKK2/NEMO complexes that are in turn required to phosphorylate and degrade IκBα allowing freed NF-κB dimers to nuclear translocation. The exact involvement of the E3 ligases, TRAF2, TRAF5, cIAP1, and cIAP2 in this process has been unclear. We summarize a recent study from our lab defining the roles of TRAF2 and cIAP1 s in activation of NF-κB downstream of TNF-R1 and report the surprising finding that RIPK1 is not essential for TNF-R1-induced NF-κB. Alternative mechanisms of how NF-κB may be activated by TNF-R1 in the light of these findings are discussed.


Ring Domain Ubiquitin Chain Death Domain Interaction Linear Ubiquitin Chain Kinase RIPK1 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank Hiroyasu Nakano for TRAF2/TRAF5 double knock-out MEFs, Robert Brink for TRAF2 conditional knock-out mice, Michelle Kelliher for RIPK1 / mice, and James Vince and Lynn Wong for their work that contributed significantly to this chapter.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of BiochemistryLa Trobe UniversityMelbourneAustralia

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