TY - JOUR
T1 - An induced proximity model for NF-κB activation in the Nod1/RICK and RIP signaling pathways
AU - Inohara, Naohiro
AU - Koseki, Takeyoshi
AU - Lin, Jingmei
AU - Del Peso, Luis
AU - Lucas, Peter C.
AU - Chen, Felicia F.
AU - Ogura, Yasunori
AU - Núñez, Gabriel
PY - 2000/9/8
Y1 - 2000/9/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034623225&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034623225&partnerID=8YFLogxK
U2 - 10.1074/jbc.M003415200
DO - 10.1074/jbc.M003415200
M3 - Article
C2 - 10880512
AN - SCOPUS:0034623225
VL - 275
SP - 27823
EP - 27831
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 36
ER -