An Induced Proximity Model for NF-κB Activation in the Nod1/RICK and RIP Signaling Pathways

By N. Inohara, T. Koseki, Jingmei Lin, L. Peso, P. Lucas, Felicia F. Chen, Y. Ogura, G. Núñez. 2000

534 citations recorded by the source corpus.

Abstract Nod1 is an Apaf-1-like molecule composed of a caspase-recruitment domain (CARD), nucleotide-binding domain, and leucine-rich repeats that associates with the CARD-containing kinase RICK and activates nuclear factor κB (NF-κB). We show that self-association of Nod1 mediates proximity of RICK and the interaction of RICK with the γ subunit of the IκB kinase (IKKγ). Similarly, the RICK-related kinase RIP associated via its intermediate region with IKKγ. A mutant form of IKKγ deficient in binding to IKKα and IKKβ inhibited NF-κB activation induced by RICK or RIP. Enforced oligomerization of RICK or RIP as well as of IKKγ, IKKα, or IKKβ was sufficient for induction of NF-κB activation. Thus, the proximity of RICK, RIP, and IKK complexes may play an important role for NF-κB activation during Nod1 oligomerization or trimerization of the tumor necrosis factor α receptor.

Subfields: Cancer Research, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/cc0ef1b2adfa5b54d68e304310580b2d55fb9ded

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. H. Nakano
2. Shizuo Akira
3. K. Takeda
4. R. Sartor

In Immunology

1. W. Strober
2. G. Núñez
3. L. Franchi
4. N. Warner
5. N. Inohara
6. A. Kitani
7. P. Murray
8. Kyle L. Viani

In Molecular Biology

1. G. Núñez
2. N. Inohara
3. L. Franchi
4. P. Murray
5. Kyle L. Viani
6. N. Warner
7. W. Strober
8. P. Dodds

Citations in the corpus

• A critical role of RICK/RIP2 polyubiquitination in Nod‐induced NF‐κB activation (2008, methodology): “…RICK-(1–292)-Fpk3-Myc, pcDNA3-RICK(K47M)-Fpk3-Myc, pcDNA3-Myc-RICK, pCGN-HA-Ub, pBxIV-luc, pcDNA3-b-gal and pMX2-puro-HA-Nod2 have been described (Inohara et al, 2000, 2003; Nishito et al, 2006). pCMV-SPORT6UBB encoding human ubiquitin B (IMAGE 4943285) was obtained from Open Biosystems…”
• Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry (2010, background): “Activation of Nod1 and Nod2 initiates a proinflammatory response dependent mainly on activation of the transcription factor NF-κB and on recruitment of the adaptor protein RIP2 (refs”
• Plant immunity: towards an integrated view of plant–pathogen interactions (2010, background): “Animal NB-containing proteins, such as NLRs and the apoptotic factors APAF1 and CED4, self-oligomerize through their centrally located NB domain after activation, thereby forming an active signalling platfor”
• Function of Nod‐like receptors in microbial recognition and host defense (2009, background): “of NF-jB kinase c (IKKc)], the regulatory subunit of IKK, and promotes its ubiquination and activation of the catalytic subunits IKKa and IKKb (46, 48).”
• Innate Immune Pattern Recognition: A Cell Biological Perspective (2015, unknown): “Upon ligand binding, NODs associate with the kinase RIPK2 via CARD domain interactions, resulting in the formation of a signaling complex that mediates NF-κβ and MAPK activation (183, 184).”
• Signalling pathways and molecular interactions of NOD1 and NOD2 (2006, background): “The postulated interaction is then proposed to initiate the activation of NOD1 and NOD2 through the induction of a complex conformational chang”