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Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti

Scholefield, J; Henriques, R; Savulescu, AF; Fontan, E; Boucharlat, A; Laplantine, E; Smahi, A; ... Mhlanga, MM; + view all (2016) Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti. Nature Communications , 7 , Article 12629. 10.1038/ncomms12629. Green open access

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Abstract

The NF-κB pathway has critical roles in cancer, immunity and inflammatory responses. Understanding the mechanism(s) by which mutations in genes involved in the pathway cause disease has provided valuable insight into its regulation, yet many aspects remain unexplained. Several lines of evidence have led to the hypothesis that the regulatory/sensor protein NEMO acts as a biological binary switch. This hypothesis depends on the formation of a higher-order structure, which has yet to be identified using traditional molecular techniques. Here we use super-resolution microscopy to reveal the existence of higher-order NEMO lattice structures dependent on the presence of polyubiquitin chains before NF-κB activation. Such structures may permit proximity-based trans-autophosphorylation, leading to cooperative activation of the signalling cascade. We further show that NF-κB activation results in modification of these structures. Finally, we demonstrate that these structures are abrogated in cells derived from incontinentia pigmenti patients.

Type: Article
Title: Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ncomms12629
Publisher version: http://doi.org/10.1038/ncomms12629
Language: English
Additional information: © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1514419
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