CASP8 cleaves N4BP1 at D424, D490

Stable Identifier
R-HSA-9757951
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
CASP8 cleaves N4BP1 at D424, D490
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
NEDD4-binding protein 1 (N4BP1) limits the activation of NF-kappaB downstream of TICAM1 (TRIF)-independent Toll-like receptor 2 (TLR2), TLR7 or TLR9 signaling pathways, but not upon engagement of TLR3 or TLR4 which utilize the adaptor protein TICAM1 (Shi H et al. 2021; Gitlin AD et al. 2020). TLR3- or TRL4-induced TICAM1-dependent activation of caspase-8 (CASP8) was found to inactivate N4BP1 via the proteolytic cleavage thus promoting NF-kappa-B activation (Gitlin AD et al. 2020; Shi H et al. 2021). Functional studies of N4BP1 mutants expressed in human embryonic kidney 293T (HEK293T) cells suggest that human N4BP1 is cleaved after D424 and/or D490 (Shi H et al. 2021).
Literature References
PubMed ID Title Journal Year
33654074 N4BP1 negatively regulates NF-κB by binding and inhibiting NEMO oligomerization

Beutler, B, Hildebrand, S, Zhan, X, Tang, M, Liu, A, Wang, Y, Quan, J, Shi, H, Anderton, P, Li, X, Ludwig, S, Moresco, EMY, Sun, L

Nat Commun 2021
Participants
Input
Output
Participates
as an event of
Event Information
Go Biological Process
regulation of I-kappaB kinase/NF-kappaB signaling (0043122)
Catalyst Activity

cysteine-type peptidase activity of active caspase-8 [cytosol]

Physical Entity
active caspase-8 [cytosol] (Homo sapiens)
Activity
cysteine-type peptidase activity (GO:0008234)
Orthologous Events
CASP8 cleaves N4BP1 at D424, D490 (Bos taurus)
CASP8 cleaves N4BP1 at D424, D490 (Canis familiaris)
CASP8 cleaves N4BP1 at D424, D490 (Danio rerio)
CASP8 cleaves N4BP1 at D424, D490 (Gallus gallus)
CASP8 cleaves N4BP1 at D424, D490 (Mus musculus)
CASP8 cleaves N4BP1 at D424, D490 (Rattus norvegicus)
CASP8 cleaves N4BP1 at D424, D490 (Sus scrofa)
Authored
Shamovsky, V  (2021-11-12)
Reviewed
de Martin, R  (2022-05-04)
D'Eustachio, P  (2022-01-05)
Created
Shamovsky, V  (2021-11-05)
Cite Us!