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Updated: Sep 9, 2025

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Optochemical control of G1 cell cycle by regulating CDK4/6 degradation

Tianyi Wang1,2,3,4, Yaming Zhang2,3,4, Yuwei Liu2,3,4

  • 1Department 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.

Iscience
|September 2, 2025
PubMed

Insights

Researchers developed a light-activated system to control cancer cell division. This optochemical strategy precisely degrades CDK4/6 proteins, offering targeted cancer therapy with fewer side effects.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Cancer progression involves cell cycle dysregulation, specifically the G1/S phase transition, often driven by CDK4/6-dependent Rb protein phosphorylation.
  • Current CDK4/6 degraders show anti-tumor potential but lack precise spatial and temporal control, leading to adverse effects.

Purpose of the Study:

  • To develop an optochemical strategy for spatiotemporal control of CDK4/6 degraders.
  • To investigate light-induced degradation of CDK4/6 proteins for targeted cancer therapy.

Main Methods:

  • Employing an optochemical approach by caging a CRBN ligand with a photoremovable protecting group.
  • Utilizing 365 nm light irradiation to trigger photocleavage and subsequent CDK4/6 degradation via the ubiquitin-proteasome system.

Main Results:

  • Achieved light-induced, spatiotemporal degradation of CDK4/6 proteins.
  • Demonstrated G1-phase cell-cycle arrest with spatial and temporal control.
  • Showcased reduced off-target effects compared to current therapies.

Conclusions:

  • The developed light-controlled system enables precise spatiotemporal degradation of CDK4/6.
  • This strategy offers enhanced specificity for cancer treatment and applications in fundamental biological research.
Keywords:
BiochemistryCancerCell biology

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