Molecular insights into the unique properties of the blood‐circulating proteasome
Abstract Proteasomes are essential for protein degradation and maintaining cellular balance, yet their roles in extracellular fluids are not well understood. Our study investigates the freely circulating proteasome in blood, to uncover its unique molecular characteristics, compared to its intracellu...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Journal of Extracellular Biology |
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| Online Access: | https://doi.org/10.1002/jex2.70034 |
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| author | Yegor Leushkin David Morgenstern Shifra Ben‐Dor Rebecca Haffner‐Krausz Katharina Zittlau Gili Ben‐Nissan Michal Sharon |
| author_facet | Yegor Leushkin David Morgenstern Shifra Ben‐Dor Rebecca Haffner‐Krausz Katharina Zittlau Gili Ben‐Nissan Michal Sharon |
| author_sort | Yegor Leushkin |
| collection | DOAJ |
| description | Abstract Proteasomes are essential for protein degradation and maintaining cellular balance, yet their roles in extracellular fluids are not well understood. Our study investigates the freely circulating proteasome in blood, to uncover its unique molecular characteristics, compared to its intracellular counterparts. Using a transgenic mouse model, mass spectrometry, and biochemical tools, we show that the predominant proteasome in serum is the free uncapped 20S particle, which seems to assemble intracellularly before entering the bloodstream. This serum proteasome is composed of constitutive and immuno subunits and exhibits all three catalytic activities. Moreover, the complex displays distinct post‐translational modifications, indicating specialization for extracellular roles, as demonstrated by its enhanced caspase‐like activity. We also found that physiological stress significantly upregulates serum 20S proteasome levels, paralleling human data. This research highlights the specialized characteristics of circulating proteasomes, offering new insights into protein turnover in the blood with significant implications for understanding proteostasis beyond the intracellular environment. |
| format | Article |
| id | doaj-art-cd196eb64c084a9d8b4a5bed90f5b285 |
| institution | Kabale University |
| issn | 2768-2811 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Biology |
| spelling | doaj-art-cd196eb64c084a9d8b4a5bed90f5b2852025-01-27T13:48:44ZengWileyJournal of Extracellular Biology2768-28112025-01-0141n/an/a10.1002/jex2.70034Molecular insights into the unique properties of the blood‐circulating proteasomeYegor Leushkin0David Morgenstern1Shifra Ben‐Dor2Rebecca Haffner‐Krausz3Katharina Zittlau4Gili Ben‐Nissan5Michal Sharon6Department of Biomolecular Sciences Weizmann Institute of Science Rehovot IsraelThe Nancy and Stephen Grand Israel National Center for Personalized Medicine Weizmann Institute of Science Rehovot IsraelBioinformatics Unit, Life Science Core Facility Weizmann Institute of Science Rehovot IsraelDepartment of Veterinary Resources Weizmann Institute of Science Rehovot IsraelDepartment of Biomolecular Sciences Weizmann Institute of Science Rehovot IsraelDepartment of Biomolecular Sciences Weizmann Institute of Science Rehovot IsraelDepartment of Biomolecular Sciences Weizmann Institute of Science Rehovot IsraelAbstract Proteasomes are essential for protein degradation and maintaining cellular balance, yet their roles in extracellular fluids are not well understood. Our study investigates the freely circulating proteasome in blood, to uncover its unique molecular characteristics, compared to its intracellular counterparts. Using a transgenic mouse model, mass spectrometry, and biochemical tools, we show that the predominant proteasome in serum is the free uncapped 20S particle, which seems to assemble intracellularly before entering the bloodstream. This serum proteasome is composed of constitutive and immuno subunits and exhibits all three catalytic activities. Moreover, the complex displays distinct post‐translational modifications, indicating specialization for extracellular roles, as demonstrated by its enhanced caspase‐like activity. We also found that physiological stress significantly upregulates serum 20S proteasome levels, paralleling human data. This research highlights the specialized characteristics of circulating proteasomes, offering new insights into protein turnover in the blood with significant implications for understanding proteostasis beyond the intracellular environment.https://doi.org/10.1002/jex2.70034bloodextracellularMass SpectrometryplasmaProteasome |
| spellingShingle | Yegor Leushkin David Morgenstern Shifra Ben‐Dor Rebecca Haffner‐Krausz Katharina Zittlau Gili Ben‐Nissan Michal Sharon Molecular insights into the unique properties of the blood‐circulating proteasome Journal of Extracellular Biology blood extracellular Mass Spectrometry plasma Proteasome |
| title | Molecular insights into the unique properties of the blood‐circulating proteasome |
| title_full | Molecular insights into the unique properties of the blood‐circulating proteasome |
| title_fullStr | Molecular insights into the unique properties of the blood‐circulating proteasome |
| title_full_unstemmed | Molecular insights into the unique properties of the blood‐circulating proteasome |
| title_short | Molecular insights into the unique properties of the blood‐circulating proteasome |
| title_sort | molecular insights into the unique properties of the blood circulating proteasome |
| topic | blood extracellular Mass Spectrometry plasma Proteasome |
| url | https://doi.org/10.1002/jex2.70034 |
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