Cactin targets the MHC class III protein IkappaB-like (IkappaBL) and inhibits NF-kappaB and interferon-regulatory factor signaling pathways
| Autor: | Niamh Curran, Paola Atzei, Paul N. Moynagh, Siobhan Gargan |
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| Rok vydání: | 2010 |
| Předmět: |
Blotting
Western Immunology Regulator Activating transcription factor Fluorescent Antibody Technique Electrophoretic Mobility Shift Assay Biochemistry Major Histocompatibility Complex MHC class I Drosophila Proteins Humans Immunoprecipitation RNA Messenger Molecular Biology Transcription factor Genetics Cell Nucleus Innate immune system biology Reverse Transcriptase Polymerase Chain Reaction Toll-Like Receptors NF-kappa B Cell Biology Acquired immune system Cell biology Interferon Regulatory Factors biology.protein I-kappa B Proteins Signal transduction Carrier Proteins Interferon regulatory factors Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 285(47) |
| ISSN: | 1083-351X |
| Popis: | Toll-like receptors (TLRs) act as primary sensors of the immune system by recognizing specific microbial motifs and inducing proinflammatory genes that facilitate innate and adaptive immunity. TLRs regulate gene expression by activating transcription factors, such as NF-κB and interferon-regulatory factors. Dysregulation of these pathways can lead to inflammatory diseases, and thus they are subject to stringent control by negative regulators of innate immune signaling. Cactin (Cactus interactor) was initially discovered as a novel interactor of Drosophila Cactus, a regulator of Drosophila Toll signaling. We now describe the first functional characterization of the human ortholog of Cactin (hCactin) and show that it acts as a negative regulator of TLRs. Overexpression of hCactin suppresses TLR-induced activation of NF-κB and interferon-regulatory factor transcription factors and induction of TLR-responsive genes, whereas knockdown of endogenous hCactin augments TLR induction of these responses. hCactin also interacts with IκB-like protein and targets other proteins that are encoded by genes in the MHC Class III region of chromosome 6. We demonstrate that hCactin localizes to the nucleus, and this nuclear localization is critical for manifesting its inhibitory effects on TLR signaling. This study thus defines hCactin as a novel negative regulator of TLR signaling and reveals its capacity to target MHC Class III genes at the molecular and functional level. |
| Databáze: | OpenAIRE |
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