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Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells

Francis, M; Bhaskar, S; Komanduri, S; Sheshadri, P; Prasanna, J; Kumar, A; (2023) Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells. iScience , 26 (5) , Article 106771. 10.1016/j.isci.2023.106771. Green open access

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Abstract

Loss of insulin-secreting β-cells in diabetes may be either due to apoptosis or dedifferentiation of β-cell mass. The ubiquitin-proteasome system comprising E3 ligase and deubiquitinases (DUBs) controls several aspects of β-cell functions. In this study, screening for key DUBs identified USP1 to be specifically involved in dedifferentiation process. Inhibition of USP1 either by genetic intervention or small-molecule inhibitor ML323 restored epithelial phenotype of β-cells, but not with inhibition of other DUBs. In absence of dedifferentiation cues, overexpression of USP1 was sufficient to induce dedifferentiation in β-cells; mechanistic insight showed USP1 to mediate its effect via modulating the expression of inhibitor of differentiation (ID) 2. In an in vivo streptozotocin (STZ)-induced dedifferentiation mouse model system, administering ML323 alleviated hyperglycemic state. Overall, this study identifies USP1 to be involved in dedifferentiation of β-cells and its inhibition may have a therapeutic application of reducing β-cell loss during diabetes.

Type: Article
Title: Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.isci.2023.106771
Publisher version: https://doi.org/10.1016/j.isci.2023.106771
Language: English
Additional information: © 2023 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
UCL classification: UCL
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10170902
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