Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells
Summary: 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 US...
| 出版年: | iScience |
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| 主要な著者: | , , , , , |
| フォーマット: | 論文 |
| 言語: | 英語 |
| 出版事項: |
Elsevier
2023-05-01
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| 主題: | |
| オンライン･アクセス: | http://www.sciencedirect.com/science/article/pii/S2589004223008489 |
| _version_ | 1851951720948563968 |
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| author | Meenal Francis Smitha Bhaskar Saarwani Komanduri Preethi Sheshadri Jyothi Prasanna Anujith Kumar |
| author_facet | Meenal Francis Smitha Bhaskar Saarwani Komanduri Preethi Sheshadri Jyothi Prasanna Anujith Kumar |
| author_sort | Meenal Francis |
| collection | DOAJ |
| container_title | iScience |
| description | Summary: 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. |
| format | Article |
| id | doaj-art-e4bf2c1186704b0691f263f5a0c93098 |
| institution | Directory of Open Access Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| spelling | doaj-art-e4bf2c1186704b0691f263f5a0c930982025-08-19T21:46:21ZengElsevieriScience2589-00422023-05-0126510677110.1016/j.isci.2023.106771Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cellsMeenal Francis0Smitha Bhaskar1Saarwani Komanduri2Preethi Sheshadri3Jyothi Prasanna4Anujith Kumar5Manipal Institute of Regenerative Medicine, Bangalore, Manipal Academy of Higher Education, Manipal, IndiaManipal Institute of Regenerative Medicine, Bangalore, Manipal Academy of Higher Education, Manipal, IndiaManipal Institute of Regenerative Medicine, Bangalore, Manipal Academy of Higher Education, Manipal, IndiaManipal Institute of Regenerative Medicine, Bangalore, Manipal Academy of Higher Education, Manipal, IndiaManipal Institute of Regenerative Medicine, Bangalore, Manipal Academy of Higher Education, Manipal, IndiaManipal Institute of Regenerative Medicine, Bangalore, Manipal Academy of Higher Education, Manipal, India; CorrespondenceSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223008489Molecular interactionDiabetologySpecialized functions of cells |
| spellingShingle | Meenal Francis Smitha Bhaskar Saarwani Komanduri Preethi Sheshadri Jyothi Prasanna Anujith Kumar Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells Molecular interaction Diabetology Specialized functions of cells |
| title | Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells |
| title_full | Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells |
| title_fullStr | Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells |
| title_full_unstemmed | Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells |
| title_short | Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells |
| title_sort | deubiquitinase usp1 influences the dedifferentiation of mouse pancreatic β cells |
| topic | Molecular interaction Diabetology Specialized functions of cells |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223008489 |
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