Kanaka Durga Devi Gorrepati
Loss of Deubiquitinase USP1 Blocks Pancreatic β-Cell Apoptosis by Inhibiting DNA Damage Response
Gorrepati, Kanaka Durga Devi; Lupse, Blaz; Annamalai, Karthika; Yuan, Ting; Maedler, Kathrin; Ardestani, Amin
Authors
Blaz Lupse
Karthika Annamalai
Ting Yuan
Kathrin Maedler
Dr Amin Ardestani A.Ardestani@hull.ac.uk
Senior Lecturer
Abstract
Impaired pancreatic β-cell survival contributes to the reduced β-cell mass in diabetes, but underlying regulatory mechanisms and key players in this process remain incompletely understood. Here, we identified the deubiquitinase ubiquitin-specific protease 1 (USP1) as an important player in the regulation of β-cell apoptosis under diabetic conditions. Genetic silencing and pharmacological suppression of USP1 blocked β-cell death in several experimental models of diabetes in vitro and ex vivo without compromising insulin content and secretion and without impairing β-cell maturation/identity genes in human islets. Our further analyses showed that USP1 inhibition attenuated DNA damage response (DDR) signals, which were highly elevated in diabetic β-cells, suggesting a USP1-dependent regulation of DDR in stressed β-cells. Our findings highlight a novel function of USP1 in the control of β-cell survival, and its inhibition may have a potential therapeutic relevance for the suppression of β-cell death in diabetes. Biochemical Mechanism; Endocrinology; Cell Biology
Citation
Gorrepati, K. D. D., Lupse, B., Annamalai, K., Yuan, T., Maedler, K., & Ardestani, A. (2018). Loss of Deubiquitinase USP1 Blocks Pancreatic β-Cell Apoptosis by Inhibiting DNA Damage Response. iScience, 1, 72-86. https://doi.org/10.1016/j.isci.2018.02.003
Journal Article Type | Article |
---|---|
Acceptance Date | Feb 1, 2018 |
Online Publication Date | Mar 23, 2018 |
Publication Date | Mar 23, 2018 |
Deposit Date | Jan 4, 2024 |
Publicly Available Date | Jan 8, 2024 |
Journal | iScience |
Print ISSN | 2589-0042 |
Electronic ISSN | 2589-0042 |
Publisher | Cell Press |
Peer Reviewed | Peer Reviewed |
Volume | 1 |
Pages | 72-86 |
DOI | https://doi.org/10.1016/j.isci.2018.02.003 |
Keywords | Biochemical mechanism; Endocrinology; Cell biology |
Public URL | https://hull-repository.worktribe.com/output/4461643 |
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Copyright Statement
© 2018 The Author(s).
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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