The death domain-containing protein Unc5CL is a novel MyD88-independent activator of the pro-inflammatory IRAK signaling cascade

Heinz, L. X., Rebsamen, M., Rossi, D. C., Staehli, F., Schroder, K., Quadroni, M., Gross, O., Schneider, P. and Tschopp, J. (2012) The death domain-containing protein Unc5CL is a novel MyD88-independent activator of the pro-inflammatory IRAK signaling cascade. Cell Death and Differentiation, 19 4: 722-731. doi:10.1038/cdd.2011.147


Author Heinz, L. X.
Rebsamen, M.
Rossi, D. C.
Staehli, F.
Schroder, K.
Quadroni, M.
Gross, O.
Schneider, P.
Tschopp, J.
Title The death domain-containing protein Unc5CL is a novel MyD88-independent activator of the pro-inflammatory IRAK signaling cascade
Journal name Cell Death and Differentiation   Check publisher's open access policy
ISSN 1350-9047
1476-5403
Publication date 2012-04
Year available 2011
Sub-type Article (original research)
DOI 10.1038/cdd.2011.147
Volume 19
Issue 4
Start page 722
End page 731
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2012
Language eng
Abstract The family of death domain (DD)-containing proteins are involved in many cellular processes, including apoptosis, inflammation and development. One of these molecules, the adapter protein MyD88, is a key factor in innate and adaptive immunity that integrates signals from the Toll-like receptor/interleukin (IL)-1 receptor (TLR/IL-1R) superfamily by providing an activation platform for IL-1R-associated kinases (IRAKs). Here we show that the DD-containing protein Unc5CL (also known as ZUD) is involved in a novel MyD88-independent mode of IRAK signaling that culminates in the activation of the transcription factor nuclear factor kappa B (NF-κB) and c-Jun N-terminal kinase. Unc5CL required IRAK1, IRAK4 and TNF receptor-associated factor 6 but not MyD88 for its ability to activate these pathways. Interestingly, the protein is constitutively autoproteolytically processed, and is anchored by its N-terminus specifically to the apical face of mucosal epithelial cells. Transcriptional profiling identified mainly chemokines, including IL-8, CXCL1 and CCL20 as Unc5CL target genes. Its prominent expression in mucosal tissues, as well as its ability to induce a pro-inflammatory program in cells, suggests that Unc5CL is a factor in epithelial inflammation and immunity as well as a candidate gene involved in mucosal diseases such as inflammatory bowel disease.
Keyword NF-kappaB
JNK
Death domain
Mucosal immunity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Advance online publication 9 December 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
 
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