K63-linked ubiquitination of RIP1 bound to the activated TLR complex

Stable Identifier
R-HSA-168915
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol, endosome membrane
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K63-linked ubiquitination of RIP1 bound to the activated TLR complex
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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.

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).

Literature References
PubMed ID Title Journal Year
21931591 cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4)

Bertrand, MJ, Lippens, S, Staes, A, Gilbert, B, Roelandt, R, De Medts, J, Gevaert, K, Declercq, W, Vandenabeele, P

PLoS ONE 2011
16603398 Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO

Ea, CK, Deng, L, Xia, ZP, Pineda, G, Chen, ZJ

Mol Cell 2006
Participants
Input
Output
Participant Of
hasEvent
Catalyst Activity
Catalyst Activity
Title
ubiquitin-protein transferase activity of RIP1 ubiqutin ligases [cytosol]
Physical Entity
RIP1 ubiqutin ligases [cytosol]
Activity
ubiquitin-protein transferase activity (0004842)
Orthologous Events
K63-linked ubiquitination of RIP1 bound to the activated TLR complex (Mus musculus)
K63-linked ubiquitination of RIP1 bound to the activated TLR complex (Sus scrofa)
Authored
de Bono, B  (2005-08-16)
Reviewed
Gay, NJ  (2006-04-24)
Gillespie, ME  (2010-11-30)
Fitzgerald, KA  (2012-11-14)
Created
de Bono, B  (2005-11-23)