Journal article icon

Journal article

Small-molecule inhibitors reveal an indispensable scaffolding role of RIPK2 in NOD2 signaling

Abstract:

RIPK2 mediates inflammatory signaling by the bacteria-sensing receptors NOD1 and NOD2. Kinase inhibitors targeting RIPK2 are a proposed strategy to ameliorate NOD-mediated pathologies. Here, we reveal that RIPK2 kinase activity is dispensable for NOD2 inflammatory signaling and show that RIPK2 inhibitors function instead by antagonizing XIAP-binding and XIAP-mediated ubiquitination of RIPK2. We map the XIAP binding site on RIPK2 to the loop between b2 and b3 of the N-lobe of the kinase, which...

Expand abstract
Publication status:
Published
Peer review status:
Peer reviewed
Version:
Publisher's Version

Actions


Access Document


Files:
Publisher copy:
10.15252/embj.201899372

Authors


More by this author
Institution:
University of Oxford
Division:
Medical Sciences
Department:
NDM; Oxford Ludwig Institute
Hdrinka, M More by this author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences
Department:
NDM; Oxford Ludwig Institute
Pinkas, DM More by this author
Expand authors...
Ludwig Institute for Cancer Research More from this funder
Publisher:
EMBO Press Publisher's website
Journal:
EMBO Journal Journal website
Volume:
37
Issue:
17
Pages:
e99372
Publication date:
2018-07-19
Acceptance date:
2018-06-22
DOI:
EISSN:
1460-2075
ISSN:
0261-4189
Pubs id:
pubs:859696
URN:
uri:155e2b9c-c475-45e1-a797-32e77edaa79e
UUID:
uuid:155e2b9c-c475-45e1-a797-32e77edaa79e
Local pid:
pubs:859696

Terms of use


Metrics



If you are the owner of this record, you can report an update to it here: Report update to this record

TO TOP