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An "In Schizo" Evaluation System to Screen for Human Kinesin-5 Inhibitors

Fara Difka Afdilla1, Woosang Hwang1, Masashi Yukawa2,3

  • 1Laboratory of Molecular and Chemical Cell Biology, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, Japan.

Methods in Molecular Biology (Clifton, N.J.)
|November 11, 2024
PubMed

Insights

A new fission yeast assay system, "in schizo," enables efficient evaluation of human kinesin-5 inhibitors. This method aids in developing novel cancer therapeutics targeting kinesin-5, addressing current drug resistance issues.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Kinesin-5 motor proteins are crucial for mitotic spindle assembly and chromosome segregation.
  • Human kinesin-5 is overexpressed in cancer cells, making it a promising target for chemotherapy.
  • Existing kinesin-5 inhibitors face challenges with efficacy and drug resistance.

Purpose of the Study:

  • To develop a novel in vivo assay system for evaluating human kinesin-5 inhibitors.
  • To facilitate the screening of more effective kinesin-5 inhibitors for cancer treatment.

Main Methods:

  • Utilized a fission yeast-based system termed "in schizo" for assessing inhibitory activity.
  • Adapted the system to monitor human kinesin-5 activity in vivo.

Main Results:

  • Successfully established a procedure to evaluate inhibitory activity against human kinesin-5.
  • Demonstrated the utility of the "in schizo" system for this purpose.

Conclusions:

  • The fission yeast "in schizo" system provides a valuable platform for developing improved kinesin-5 inhibitors.
  • This approach can be extended to screen for inhibitors targeting other human cancer-related proteins.
Keywords:
Diffusion assayEg5 inhibitorKinesin-5PCRYeast transformationnmt1 promotor

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