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Deregulated AUF1 Assists BMP-EZH2-Mediated Delayed Wound Healing during Candida albicans Infection

Mahadik, Kasturi and Yadav, Preeti and Bhatt, Bharat and Shah, Riyaz Ahmad and Balaji, Kithiganahalli Narayanaswamy (2018) Deregulated AUF1 Assists BMP-EZH2-Mediated Delayed Wound Healing during Candida albicans Infection. In: JOURNAL OF IMMUNOLOGY, 201 (12). pp. 3617-3629.

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Official URL: https://doi.org/10.4049/jimmunol.1800688


Tissue repair is a complex process that necessitates an interplay of cellular processes, now known to be dictated by epigenetics. Intriguingly, macrophages are testimony to a large repertoire of evolving functions in this process. We identified a role for BMP signaling in regulating macrophage responses to Candida albicans infection during wound repair in a murine model. In this study, the RNA binding protein, AU-rich element-binding factor 1, was posttranslationally destabilized to bring about ubiquitin ligase, NEDD4-directed activation of BMP signaling. Concomitantly, PI3K/PKC delta mobilized the rapid phosphorylation of BMP-responsive Smad1/5/8. Activated BMP pathway orchestrated the elevated recruitment of EZH2 at promoters of genes assisting timely wound closure. In vivo, the repressive H3K27 trimethylation was observed to persist, accompanied by a robust upregulation of BMP pathway upon infection with C. albicans, culminating in delayed wound healing. Altogether, we uncovered the signaling networks coordinated by fungal colonies that are now increasingly associated with the infected wound microbiome, resulting in altered wound fate.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to AMER ASSOC IMMUNOLOGISTS
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 10 Feb 2019 04:33
Last Modified: 10 Feb 2019 04:33
URI: http://eprints.iisc.ac.in/id/eprint/61348

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