The ubiquitin-proteasome system in circadian regulation
To align sleep–wake behavior and internal physiology with the Earth’s 24-h light–dark cycle, organisms rely on circadian clocks–endogenous timekeeping systems that anticipate and adapt to daily environmental changes. These clocks are governed by transcription-translation feedback loops that produce...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2025.1632905/full |
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| author | Kara M. Costanzo Matthew V. Prifti Sokol V. Todi Sokol V. Todi Ryan D. Mohan |
| author_facet | Kara M. Costanzo Matthew V. Prifti Sokol V. Todi Sokol V. Todi Ryan D. Mohan |
| author_sort | Kara M. Costanzo |
| collection | DOAJ |
| description | To align sleep–wake behavior and internal physiology with the Earth’s 24-h light–dark cycle, organisms rely on circadian clocks–endogenous timekeeping systems that anticipate and adapt to daily environmental changes. These clocks are governed by transcription-translation feedback loops that produce rhythmic oscillations in gene expression, including key regulators such as PERIOD and CRYPTOCHROME. The timing and stability of these proteins are tightly controlled by post-translational mechanisms, including ubiquitin-mediated degradation. The ubiquitin-proteasome system (UPS) ensures that clock proteins are cleared at precise times within the circadian cycle, a process which is essential for resetting the molecular clock and sustaining robust circadian rhythms. Disruption of this process can have profound impacts on human health and contribute to impairments in sleep timing, circadian phase, and rhythm amplitude. In this review, we focus on the mechanistic role of the UPS in circadian clock regulation, summarize key E3 ligases and deubiquitinating enzymes implicated in clock protein turnover, and highlight the essential role of the UPS on sleep timing and overall circadian biological homeostasis. |
| format | Article |
| id | doaj-art-a64f4837e0cf4a6693ba5b8954fe2b87 |
| institution | Kabale University |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj-art-a64f4837e0cf4a6693ba5b8954fe2b872025-08-26T05:28:08ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-08-011910.3389/fnins.2025.16329051632905The ubiquitin-proteasome system in circadian regulationKara M. Costanzo0Matthew V. Prifti1Sokol V. Todi2Sokol V. Todi3Ryan D. Mohan4Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United StatesDepartment of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United StatesDepartment of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United StatesDepartment of Neurology, Wayne State University School of Medicine, Detroit, MI, United StatesDepartment of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United StatesTo align sleep–wake behavior and internal physiology with the Earth’s 24-h light–dark cycle, organisms rely on circadian clocks–endogenous timekeeping systems that anticipate and adapt to daily environmental changes. These clocks are governed by transcription-translation feedback loops that produce rhythmic oscillations in gene expression, including key regulators such as PERIOD and CRYPTOCHROME. The timing and stability of these proteins are tightly controlled by post-translational mechanisms, including ubiquitin-mediated degradation. The ubiquitin-proteasome system (UPS) ensures that clock proteins are cleared at precise times within the circadian cycle, a process which is essential for resetting the molecular clock and sustaining robust circadian rhythms. Disruption of this process can have profound impacts on human health and contribute to impairments in sleep timing, circadian phase, and rhythm amplitude. In this review, we focus on the mechanistic role of the UPS in circadian clock regulation, summarize key E3 ligases and deubiquitinating enzymes implicated in clock protein turnover, and highlight the essential role of the UPS on sleep timing and overall circadian biological homeostasis.https://www.frontiersin.org/articles/10.3389/fnins.2025.1632905/fullubiquitinationdeubiquitinationtranscriptional regulationmolecular clockprotein homeostasis |
| spellingShingle | Kara M. Costanzo Matthew V. Prifti Sokol V. Todi Sokol V. Todi Ryan D. Mohan The ubiquitin-proteasome system in circadian regulation Frontiers in Neuroscience ubiquitination deubiquitination transcriptional regulation molecular clock protein homeostasis |
| title | The ubiquitin-proteasome system in circadian regulation |
| title_full | The ubiquitin-proteasome system in circadian regulation |
| title_fullStr | The ubiquitin-proteasome system in circadian regulation |
| title_full_unstemmed | The ubiquitin-proteasome system in circadian regulation |
| title_short | The ubiquitin-proteasome system in circadian regulation |
| title_sort | ubiquitin proteasome system in circadian regulation |
| topic | ubiquitination deubiquitination transcriptional regulation molecular clock protein homeostasis |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2025.1632905/full |
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