Protein degradation of Lsd1 is mediated by Bre1 yet opposed by Lsd1-interacting lncRNAs during fly follicle development
Summary: Tissue development, homeostasis, and repair all require efficient progenitor expansion. Lysine-specific demethylase 1 (Lsd1) maintains plastic epigenetic states to promote progenitor proliferation while overexpressed Lsd1 protein causes oncogenic gene expression in cancer cells. However, th...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-05-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224009052 |
| _version_ | 1827277704522629120 |
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| author | Chun Ting Lin Ruei-Teng Ting Yang-Hsuan Ou Tzu-Ling Shao Ming-Chia Lee |
| author_facet | Chun Ting Lin Ruei-Teng Ting Yang-Hsuan Ou Tzu-Ling Shao Ming-Chia Lee |
| author_sort | Chun Ting Lin |
| collection | DOAJ |
| description | Summary: Tissue development, homeostasis, and repair all require efficient progenitor expansion. Lysine-specific demethylase 1 (Lsd1) maintains plastic epigenetic states to promote progenitor proliferation while overexpressed Lsd1 protein causes oncogenic gene expression in cancer cells. However, the precise regulation of Lsd1 protein expression at the molecular level to drive progenitor differentiation remains unclear. Here, using Drosophila melanogaster oogenesis as our experimental system, we discovered molecular machineries that modify Lsd1 protein stability in vivo. Through genetic and biochemical analyses, an E3 ubiquitin ligase, Bre1, was identified as required for follicle progenitor differentiation, likely by mediating Lsd1 protein degradation. Interestingly, specific Lsd1-interacting long non-coding RNAs (LINRs) were found to antagonize Bre1-mediated Lsd1 protein degradation. The intricate interplay discovered among the Lsd1 complex, LINRs and Bre1 provides insight into how Lsd1 protein stability is fine-tuned to underlie progenitor differentiation in vivo. |
| first_indexed | 2024-04-24T07:37:44Z |
| format | Article |
| id | doaj.art-c83d88ba382d48ed8c688f8e701bb034 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-24T07:37:44Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-c83d88ba382d48ed8c688f8e701bb0342024-04-20T04:17:44ZengElsevieriScience2589-00422024-05-01275109683Protein degradation of Lsd1 is mediated by Bre1 yet opposed by Lsd1-interacting lncRNAs during fly follicle developmentChun Ting Lin0Ruei-Teng Ting1Yang-Hsuan Ou2Tzu-Ling Shao3Ming-Chia Lee4Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan; Info & Research Bldg, Rm 904, #155, Sec. 2, Li-Nong St, Taipei City 112, TaiwanDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan; Info & Research Bldg, Rm 904, #155, Sec. 2, Li-Nong St, Taipei City 112, TaiwanDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan; Info & Research Bldg, Rm 904, #155, Sec. 2, Li-Nong St, Taipei City 112, TaiwanDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan; Info & Research Bldg, Rm 904, #155, Sec. 2, Li-Nong St, Taipei City 112, TaiwanDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan; Info & Research Bldg, Rm 904, #155, Sec. 2, Li-Nong St, Taipei City 112, Taiwan; Corresponding authorSummary: Tissue development, homeostasis, and repair all require efficient progenitor expansion. Lysine-specific demethylase 1 (Lsd1) maintains plastic epigenetic states to promote progenitor proliferation while overexpressed Lsd1 protein causes oncogenic gene expression in cancer cells. However, the precise regulation of Lsd1 protein expression at the molecular level to drive progenitor differentiation remains unclear. Here, using Drosophila melanogaster oogenesis as our experimental system, we discovered molecular machineries that modify Lsd1 protein stability in vivo. Through genetic and biochemical analyses, an E3 ubiquitin ligase, Bre1, was identified as required for follicle progenitor differentiation, likely by mediating Lsd1 protein degradation. Interestingly, specific Lsd1-interacting long non-coding RNAs (LINRs) were found to antagonize Bre1-mediated Lsd1 protein degradation. The intricate interplay discovered among the Lsd1 complex, LINRs and Bre1 provides insight into how Lsd1 protein stability is fine-tuned to underlie progenitor differentiation in vivo.http://www.sciencedirect.com/science/article/pii/S2589004224009052BiochemistryMolecular mechanism of gene regulationDevelopmental biology |
| spellingShingle | Chun Ting Lin Ruei-Teng Ting Yang-Hsuan Ou Tzu-Ling Shao Ming-Chia Lee Protein degradation of Lsd1 is mediated by Bre1 yet opposed by Lsd1-interacting lncRNAs during fly follicle development iScience Biochemistry Molecular mechanism of gene regulation Developmental biology |
| title | Protein degradation of Lsd1 is mediated by Bre1 yet opposed by Lsd1-interacting lncRNAs during fly follicle development |
| title_full | Protein degradation of Lsd1 is mediated by Bre1 yet opposed by Lsd1-interacting lncRNAs during fly follicle development |
| title_fullStr | Protein degradation of Lsd1 is mediated by Bre1 yet opposed by Lsd1-interacting lncRNAs during fly follicle development |
| title_full_unstemmed | Protein degradation of Lsd1 is mediated by Bre1 yet opposed by Lsd1-interacting lncRNAs during fly follicle development |
| title_short | Protein degradation of Lsd1 is mediated by Bre1 yet opposed by Lsd1-interacting lncRNAs during fly follicle development |
| title_sort | protein degradation of lsd1 is mediated by bre1 yet opposed by lsd1 interacting lncrnas during fly follicle development |
| topic | Biochemistry Molecular mechanism of gene regulation Developmental biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224009052 |
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