Optochemical control of G1 cell cycle by regulating CDK4/6 degradation
Summary: Cancer progression is characterized by dysregulated G1/S phase transition mediated by CDK4/6-dependent Rb protein phosphorylation. Although CDK4/6 degraders show encouraging anti-tumor efficacy, it is highly desired to develop strategies to spatiotemporally control the release of active CDK...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225015652 |
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| author | Tianyi Wang Yaming Zhang Yuwei Liu Lichao Wang Lijun Liu Weiping Wang |
| author_facet | Tianyi Wang Yaming Zhang Yuwei Liu Lichao Wang Lijun Liu Weiping Wang |
| author_sort | Tianyi Wang |
| collection | DOAJ |
| description | Summary: Cancer progression is characterized by dysregulated G1/S phase transition mediated by CDK4/6-dependent Rb protein phosphorylation. Although CDK4/6 degraders show encouraging anti-tumor efficacy, it is highly desired to develop strategies to spatiotemporally control the release of active CDK4/6 degraders to further reduce adverse effects. In this study, we employ an optochemical strategy for CDK4/6 degradation by caging the CRBN ligand with a photoremovable protecting group. Light irradiation at 365 nm triggers photocleavage, thereby inducing CDK4/6 degradation via the ubiquitin-proteasome system. The resultant G1-phase arrest demonstrates spatial and temporal control over cell-cycle progression, reducing off-target effects of current therapies. This light-controlled system allows spatiotemporal CDK4/6 degradation and G1 cell-cycle arrest, providing a promising strategy to enhance specificity for cancer treatment and fundamental biological research. |
| format | Article |
| id | doaj-art-427fc4602ade43bc9216347b97c7f283 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-427fc4602ade43bc9216347b97c7f2832025-08-23T04:48:54ZengElsevieriScience2589-00422025-09-0128911330410.1016/j.isci.2025.113304Optochemical control of G1 cell cycle by regulating CDK4/6 degradationTianyi Wang0Yaming Zhang1Yuwei Liu2Lichao Wang3Lijun Liu4Weiping Wang5Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou 510060, China; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong, ChinaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong, ChinaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong, ChinaNational Frontiers Science Center for Industrial Intelligence and Systems Optimization, Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang 110819, ChinaNational Frontiers Science Center for Industrial Intelligence and Systems Optimization, Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang 110819, ChinaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong, China; Corresponding authorSummary: Cancer progression is characterized by dysregulated G1/S phase transition mediated by CDK4/6-dependent Rb protein phosphorylation. Although CDK4/6 degraders show encouraging anti-tumor efficacy, it is highly desired to develop strategies to spatiotemporally control the release of active CDK4/6 degraders to further reduce adverse effects. In this study, we employ an optochemical strategy for CDK4/6 degradation by caging the CRBN ligand with a photoremovable protecting group. Light irradiation at 365 nm triggers photocleavage, thereby inducing CDK4/6 degradation via the ubiquitin-proteasome system. The resultant G1-phase arrest demonstrates spatial and temporal control over cell-cycle progression, reducing off-target effects of current therapies. This light-controlled system allows spatiotemporal CDK4/6 degradation and G1 cell-cycle arrest, providing a promising strategy to enhance specificity for cancer treatment and fundamental biological research.http://www.sciencedirect.com/science/article/pii/S2589004225015652BiochemistryCell biologyCancer |
| spellingShingle | Tianyi Wang Yaming Zhang Yuwei Liu Lichao Wang Lijun Liu Weiping Wang Optochemical control of G1 cell cycle by regulating CDK4/6 degradation iScience Biochemistry Cell biology Cancer |
| title | Optochemical control of G1 cell cycle by regulating CDK4/6 degradation |
| title_full | Optochemical control of G1 cell cycle by regulating CDK4/6 degradation |
| title_fullStr | Optochemical control of G1 cell cycle by regulating CDK4/6 degradation |
| title_full_unstemmed | Optochemical control of G1 cell cycle by regulating CDK4/6 degradation |
| title_short | Optochemical control of G1 cell cycle by regulating CDK4/6 degradation |
| title_sort | optochemical control of g1 cell cycle by regulating cdk4 6 degradation |
| topic | Biochemistry Cell biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225015652 |
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