K63-polyubiquitin RIP1:TRIF:activated TLR3/TLR4 activated TLR4/TLR3:TRIF:K63-pUb-RIP1 K63-linked ubiquitination of RIP1 bound to the activated TLR complex Authored: de Bono, B, 2005-08-16 10:54:15 EC Number: 6.3.2.19 Edited: Shamovsky, V, 2011-08-12 Pubmed11479302 Pubmed15064760 Pubmed15258597 Pubmed16115877 Pubmed16547522 Pubmed16603398 Pubmed21931591 RIP1 polyubiquitination was induced upon TNF- or poly(I-C) treatment of the macrophage cell line RAW264.7 and the U373 astrocytoma line (Cusson-Hermance et al 2005). These workers have suggested that RIP1 may use similar mechanisms to induce NF-kB in the TNFR1- and Trif-dependent TLR pathways.<p>RIP1 modification with Lys-63 polyubiquitin chains was shown to be essential for TNF-induced activation of NF-kB (Ea et al. 2006). It is thought that TRAF family members mediate this Lys63-linked ubiquitination of RIP1 (Wertz et al. 2004, Tada et al 2001, Vallabhapurapu and Karin 2009), which may facilitate recruitment of the TAK1 complex and thus activation of NF-kB. Binding of NEMO to Lys63-linked polyubiquitinated RIP1 is also required in the signaling cascade from the activated receptor to the IKK-mediated NF-kB activation (Wu et al. 2006). Reactome Database ID Release 43168915 Reactome, http://www.reactome.org ReactomeREACT_6884 Reviewed: Fitzgerald, Katherine A, 2012-11-13 Reviewed: Gay, NJ, 2006-04-24 16:48:17 Reviewed: Gillespie, ME, 2010-11-30 has a Stoichiometric coefficient of 2