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

Stable Identifier
Reaction [transition]
Homo sapiens
Related Species
Influenza A virus, Rotavirus, Hepatitis B virus, Hepatitis C Virus, Human herpesvirus 1
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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
16603398 Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO

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

Mol Cell 2006
21931591 cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4)

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

PLoS ONE 2011
15064760 RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B

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

Nat Immunol 2004
Catalyst Activity

ubiquitin-protein transferase activity of RIP1 ubiqutin ligases [cytosol]

Cite Us!