| The death domain-containing protein Unc5CL is a novel MyD88-independent activator of the pro-inflammatory IRAK signaling cascade. | |
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MedLine Citation:
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PMID: 22158417 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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.Cell Death and Differentiation advance online publication, 9 December 2011; doi:10.1038/cdd.2011.147. |
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Authors:
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L X Heinz; M Rebsamen; D C Rossi; F Staehli; K Schroder; M Quadroni; O Gross; P Schneider; J Tschopp |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-09 |
Journal Detail:
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Title: Cell death and differentiation Volume: - ISSN: 1476-5403 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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