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DC Field | Value | Language |
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dc.contributor.author | Kliza, K | - |
dc.contributor.author | Song, W | - |
dc.contributor.author | Pinzuti, I | - |
dc.contributor.author | Schaubeck, S | - |
dc.contributor.author | Kunzelmann, S | - |
dc.contributor.author | Kuntin, D | - |
dc.contributor.author | Fornili, A | - |
dc.contributor.author | Pandini, A | - |
dc.contributor.author | Hofmann, K | - |
dc.contributor.author | Garnett, JA | - |
dc.contributor.author | Stieglitz, B | - |
dc.contributor.author | Husnjak, K | - |
dc.date.accessioned | 2024-08-11T10:43:59Z | - |
dc.date.available | 2024-08-11T10:43:59Z | - |
dc.date.issued | 2021-11-02 | - |
dc.identifier | ORCiD: Alessandro Pandini https://orcid.org/0000-0002-4158-233X | - |
dc.identifier.citation | Kliza, K. et al. (2021) 'N4BP1 is dimerization-dependent linear ubiquitin reader regulating TNFR1 signalling through linear ubiquitin binding and Caspase-8-mediated processing', bioRxiv preprint, pp. 1 - 35. doi: 10.1101/2021.11.02.466974. | en_US |
dc.identifier.issn | 2692-8205 | - |
dc.identifier.uri | https://bura.brunel.ac.uk/handle/2438/29532 | - |
dc.description | This article is a preprint and has not been certified by peer review. | en_US |
dc.description | Data and material availability: All the plasmids generated in this study will be available upon request. All data is available in the main text or the supplementary materials online at: https://doi.org/10.1101/2021.11.02.466974 .. | - |
dc.description.abstract | Signalling through TNFR1 modulates proinflammatory gene transcription and programmed cell death, and its impairment causes autoimmune diseases and cancer. NEDD4-binding protein 1 (N4BP1) was recently identified as a critical suppressor of proinflammatory cytokine production1, whose mode of action remained unknown. Here, we show that N4BP1 is a novel linear ubiquitin reader that negatively regulates NFκB signalling by its unique dimerizationdependent ubiquitin-binding module that we named LUBIN. Dimeric N4BP1 strategically positions two non-selective ubiquitin-binding domains to ensure exclusive recognition of linear ubiquitin. Under proinflammatory conditions, N4BP1 is recruited to the nascent TNFR1 signalling complex, where it regulates duration of proinflammatory signalling in LUBIN-dependent manner. N4BP1 deficiency accelerates TNFα-induced cell death by increasing complex II assembly. Under proapoptotic conditions, Caspase-8 mediates proteolytic processing of N4BP1 and the resulting cleavage fragment of N4BP1, which retains the ability to bind linear ubiquitin, is rapidly degraded by the 26S proteasome, accelerating apoptosis. In summary, our findings demonstrate that N4BP1 dimerization creates a unique linear ubiquitin reader that ensures timely and coordinated regulation of TNFR1-mediated inflammation and cell death. | en_US |
dc.description.sponsorship | This work was supported by the Francis Crick Institute through provision of access to the MRC Biomedical NMR Centre. The Francis Crick Institute receives its core funding from Cancer Research UK (FC001029), the UK Medical Research Council (FC001029), and the Wellcome Trust (FC001029). KK was supported by the UPStream grant (EU, FP7, ITN project 290257). | en_US |
dc.format.extent | 1 - 35 | - |
dc.format.medium | Electronic | - |
dc.language.iso | en_US | en_US |
dc.publisher | Cold Spring Harbor Laboratory | en_US |
dc.rights | Copyright © 2021 The Authors. The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. | - |
dc.title | N4BP1 is dimerization-dependent linear ubiquitin reader regulating TNFR1 signalling through linear ubiquitin binding and Caspase-8-mediated processing | en_US |
dc.type | Article | en_US |
dc.date.dateAccepted | 2021-11-02 | - |
dc.identifier.doi | https://doi.org/10.1101/2021.11.02.466974 | - |
pubs.publication-status | Published online | - |
dc.rights.holder | The Authors | - |
Appears in Collections: | Dept of Computer Science Research Papers |
Files in This Item:
File | Description | Size | Format | |
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Preprint.pdf | Copyright © 2021 The Authors. The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. | 10.76 MB | Adobe PDF | View/Open |
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