Reactome | TRAF2:TRAF1:cIAP1,2:TRAF3:NIK regulatory complex binds CD40

TRAF2:TRAF1:cIAP1,2:TRAF3:NIK regulatory complex binds CD40

Stable Identifier

R-HSA-5676597

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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TRAF2:TRAF1:cIAP1,2:TRAF3:NIK regulatory complex binds CD40

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After its ligation with CD40 ligand (CD40L), CD40 is activated and triggers direct recruitment of multiple TRAF proteins and initiate non-canonical NF-kB pathway. TRAF1, TRAF2, TRAF3, and TRAF6, but not TRAF4 or TRAF5, shown to bind directly to the CD40 cytoplasmic domain (Pullen et al. 1998). TRAF2 is part of the regulatory complex which includes cellular inhibitor of apoptosis (cIAP) 1 and 2 and which in turn interacts with TRAF3 and NFkB-inducing kinase (NIK). In unstimulated cells this regulatory complex acts as a negative regulator of non-canonical NFkB pathway by constantly degrading NIK, whereas up on recruitment to CD40 this complex leads to accumulation of NIK (Elgueta et al. 2009, Schonbeck & Libby 2001).

Literature References

PubMed ID	Title	Journal	Year
12374738	CD40 regulates the processing of NF-kappaB2 p100 to p52 Holman, MJ, Coope, HJ, Huhse, B, Atkinson, PG, Klaus, GG, Ley, SC, Johnston, LH, Belich, M, Janzen, J	EMBO J.	2002
9718306	CD40-tumor necrosis factor receptor-associated factor (TRAF) interactions: regulation of CD40 signaling through multiple TRAF binding sites and TRAF hetero-oligomerization Dang, TT, Everdeen, DS, Crute, JJ, Kehry, MR, Miller, HG, Pullen, SS	Biochemistry	1998
24298274	CD40-Mediated Activation of the NF-?B2 Pathway Bishop, GA, Hostager, BS	Front Immunol	2013
19426221	Molecular mechanism and function of CD40/CD40L engagement in the immune system Noelle, RJ, Wasiuk, A, Elgueta, R, Benson, MJ, de Vries, VC, Guo, Y	Immunol. Rev.	2009