Related Experiment Video

Updated: Dec 31, 2025

Author Spotlight: Establishing CENP-E Knockout HeLa Cells – A Novel Approach to Study Kinesin-7 CENP-E Biology and its Inhibitors
11:49

Author Spotlight: Establishing CENP-E Knockout HeLa Cells – A Novel Approach to Study Kinesin-7 CENP-E Biology and its Inhibitors

Published on: June 23, 2023

1.1K

Photoswitchable CENP-E Inhibitor Enabling the Dynamic Control of Chromosome Movement and Mitotic Progression

Noushaba Nusrat Mafy1, Kazuya Matsuo1, Shota Hiruma2

  • 1Research Institute for Electronic Science , Hokkaido University , Kita 20, Nishi 10 , Kita-ku, Sapporo , 001-0020 , Japan.

Journal of the American Chemical Society
|January 14, 2020
PubMed

Insights

This study introduces a light-controlled inhibitor for CENP-E, a key protein in cell division. This photoswitchable drug offers precise control over mitosis, potentially leading to safer and more effective cancer therapies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Interfering with mitosis is a promising cancer therapy strategy.
  • Current antimitotic drugs lack precise control, leading to significant side effects.
  • CENP-E, a mitotic kinesin, is crucial for chromosome transport during cell division.

Purpose of the Study:

  • To develop a photoswitchable inhibitor for CENP-E.
  • To achieve precise, light-controlled interference with mitosis.
  • To explore the precise functions of CENP-E in cellular processes.

Main Methods:

  • Development of an azobenzene-based photoswitchable CENP-E inhibitor.
  • In vitro and in vivo assessment of inhibitor activity and photoswitching.
  • UV/vis light illumination cycles to control inhibitor activity and observe effects on chromosome congression and mitotic progression.

Main Results:

  • The inhibitor demonstrated reversible photoswitching of CENP-E activity with a ~10-fold change in IC50 between cis and trans states.
  • Repeatable photoswitching of chromosome congression and mitotic progression was achieved using light.
  • The study precisely identified the role of CENP-E in specific stages of mitotic progression.

Conclusions:

  • A photochemical approach enables highly controllable interference with mitosis.
  • This method allows for the discovery of precise molecular functions in dynamic cellular processes.
  • The developed photoswitchable inhibitor holds potential for targeted cancer therapy with reduced side effects.

More Related Videos

Functional Assessment of Kinesin-7 CENP-E in Spermatocytes Using In Vivo Inhibition, Immunofluorescence and Flow Cytometry09:41

Functional Assessment of Kinesin-7 CENP-E in Spermatocytes Using In Vivo Inhibition, Immunofluorescence and Flow Cytometry

Published on: December 28, 2021

2.1K
Spatiotemporal Subcellular Manipulation of the Microtubule Cytoskeleton in the Living Preimplantation Mouse Embryo using Photostatins08:13

Spatiotemporal Subcellular Manipulation of the Microtubule Cytoskeleton in the Living Preimplantation Mouse Embryo using Photostatins

Published on: November 30, 2021

2.8K

Related Concept Videos

Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
4.2K
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.6K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.3K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.5K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.2K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
6.4K