Nod2-Nodosome in a Cell-Free System: Implications in Pathogenesis and Drug Discovery for Blau Syndrome and Early-Onset Sarcoidosis
Joint Authors
Kawakami, Atsushi
Migita, Kiyoshi
Iwasaki, Tomoyuki
Kaneko, Naoe
Ito, Yuki
Takeda, Hiroyuki
Sawasaki, Tatsuya
Heike, Toshio
Agematsu, Kazunaga
Morikawa, Shinnosuke
Mokuda, Sho
Kurata, Mie
Masumoto, Junya
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-7, 7 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-06-15
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Medicine
Information Technology and Computer Science
Abstract EN
Nucleotide-binding oligomerization domain-containing protein (Nod) 2 is an intracellular pattern recognition receptor, which recognizes muramyl dipeptide (N-Acetylmuramyl-L-Alanyl-D-Isoglutamine: MDP), a bacterial peptidoglycan component, and makes a NF-κB-activating complex called nodosome with adaptor protein RICK (RIP2/RIPK2).
Nod2 mutants are associated with the autoinflammatory diseases, Blau syndrome (BS)/early-onset sarcoidosis (EOS).
For drug discovery of BS/EOS, we tried to develop Nod2-nodosome in a cell-free system.
FLAG-tagged RICK, biotinylated-Nod2, and BS/EOS-associated Nod2 mutants were synthesized, and proximity signals between FLAG-tagged and biotinylated proteins were detected by amplified luminescent proximity homogeneous assay (ALPHA).
Upon incubation with MDP, the ALPHA signal of interaction between Nod2-WT and RICK was increased in a dose-dependent manner.
The ALPHA signal of interaction between RICK and the BS/EOS-associated Nod2 mutants was more significantly increased than Nod2-WT.
Notably, the ALPHA signal between Nod2-WT and RICK was increased upon incubation with MDP, but not when incubated with the same concentrations, L-alanine, D-isoglutamic acid, or the MDP-D-isoform.
Thus, we successfully developed Nod2-nodosome in a cell-free system reflecting its function in vivo, and it can be useful for screening Nod2-nodosome-targeted therapeutic molecules for BS/EOS and granulomatous inflammatory diseases.
American Psychological Association (APA)
Iwasaki, Tomoyuki& Kaneko, Naoe& Ito, Yuki& Takeda, Hiroyuki& Sawasaki, Tatsuya& Heike, Toshio…[et al.]. 2016. Nod2-Nodosome in a Cell-Free System: Implications in Pathogenesis and Drug Discovery for Blau Syndrome and Early-Onset Sarcoidosis. The Scientific World Journal،Vol. 2016, no. 2016, pp.1-7.
https://search.emarefa.net/detail/BIM-1120350
Modern Language Association (MLA)
Iwasaki, Tomoyuki…[et al.]. Nod2-Nodosome in a Cell-Free System: Implications in Pathogenesis and Drug Discovery for Blau Syndrome and Early-Onset Sarcoidosis. The Scientific World Journal No. 2016 (2016), pp.1-7.
https://search.emarefa.net/detail/BIM-1120350
American Medical Association (AMA)
Iwasaki, Tomoyuki& Kaneko, Naoe& Ito, Yuki& Takeda, Hiroyuki& Sawasaki, Tatsuya& Heike, Toshio…[et al.]. Nod2-Nodosome in a Cell-Free System: Implications in Pathogenesis and Drug Discovery for Blau Syndrome and Early-Onset Sarcoidosis. The Scientific World Journal. 2016. Vol. 2016, no. 2016, pp.1-7.
https://search.emarefa.net/detail/BIM-1120350
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1120350