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

Stable Identifier
R-HSA-9014342
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Rotavirus, Influenza A virus, Hepatitis B virus, Hepatitis C Virus, Human herpesvirus 1
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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
15064760 RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B

Meylan, E, Burns, K, Hofmann, K, Blancheteau, V, Martinon, F, Kelliher, M, Tschopp, J

Nat Immunol 2004
Participants
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Catalyst Activity
Catalyst Activity
Title
ubiquitin-protein transferase activity of RIP1 ubiqutin ligases [cytosol]
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Activity
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Created