Functional genomics identifies negative regulatory nodes controlling phagocyte oxidative burst

DSpace/Manakin Repository

Functional genomics identifies negative regulatory nodes controlling phagocyte oxidative burst

Citable link to this page

 

 
Title: Functional genomics identifies negative regulatory nodes controlling phagocyte oxidative burst
Author: Graham, Daniel B.; Becker, Christine E.; Doan, Aivi; Goel, Gautam; Villablanca, Eduardo J.; Knights, Dan; Mok, Amanda; Ng, Aylwin C.Y.; Doench, John G.; Root, David E.; Clish, Clary B.; Xavier, Ramnik J.

Note: Order does not necessarily reflect citation order of authors.

Citation: Graham, D. B., C. E. Becker, A. Doan, G. Goel, E. J. Villablanca, D. Knights, A. Mok, et al. 2015. “Functional genomics identifies negative regulatory nodes controlling phagocyte oxidative burst.” Nature Communications 6 (1): 7838. doi:10.1038/ncomms8838. http://dx.doi.org/10.1038/ncomms8838.
Full Text & Related Files:
Abstract: The phagocyte oxidative burst, mediated by Nox2 NADPH oxidase-derived reactive oxygen species, confers host defense against a broad spectrum of bacterial and fungal pathogens. Loss-of-function mutations that impair function of the Nox2 complex result in a life-threatening immunodeficiency, and genetic variants of Nox2 subunits have been implicated in pathogenesis of inflammatory bowel disease (IBD). Thus, alterations in the oxidative burst can profoundly impact host defense, yet little is known about regulatory mechanisms that fine-tune this response. Here we report the discovery of regulatory nodes controlling oxidative burst by functional screening of genes within loci linked to human inflammatory disease. Implementing a multi-omics approach, we define transcriptional, metabolic and ubiquitin-cycling nodes controlled by Rbpj, Pfkl and Rnf145, respectively. Furthermore, we implicate Rnf145 in proteostasis of the Nox2 complex by endoplasmic reticulum-associated degradation. Consequently, ablation of Rnf145 in murine macrophages enhances bacterial clearance, and rescues the oxidative burst defects associated with Ncf4 haploinsufficiency.
Published Version: doi:10.1038/ncomms8838
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518307/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:21462071
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters