Atzei, Paola and Gargan, Siobhan and Curran, Niamh and Moynagh, Paul N. (2010) Cactin Targets the MHC Class III Protein IκB-like (IκBL) and Inhibits NF-κB and Interferon-regulatory Factor Signaling Pathways. Journal of Biological Chemistry, 285 (47). pp. 36804-36817. ISSN 0021-9258

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Abstract

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.Wenow 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 TLRinduced 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 IκBlike 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.

Item Type:	Article
Additional Information:	This work was funded by Science Foundation Ireland Grant SFI/RFP/ BIC1501, the Health Research Board of Ireland, and the European Union Marie Curie Action (MNIEST). This research was originally published in the Journal of Biological Chemistry. Paola Atzei, Siobhan Gargan, Niamh Curran, and Paul N. Moynagh. Cactin Targets the MHC Class III Protein IκB-like (IκBL) and Inhibits NF-κB and Interferon-regulatory Factor Signaling Pathways. Journal of Biological Chemistry. 2010; 285:36804-36817. © the American Society for Biochemistry and Molecular Biology.
Keywords:	Cactin; MHC Class III Protein IκB-like; IκBL; Inhibit; NF-κB; Interferon-regulatory Factor; Signaling Pathways; Toll-like receptors; immunity;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	7186
Identification Number:	https://doi.org/10.1074/jbc.M110.139113
Depositing User:	Professor Paul Moynagh
Date Deposited:	15 Jul 2016 11:07
Journal or Publication Title:	Journal of Biological Chemistry
Publisher:	American Society for Biochemistry and Molecular Biology
Refereed:	Yes
Funders:	Science Foundation Ireland (SFI), Health Research Board (HRB), European Union Marie Curie Action (MNIEST)
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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