Related Experiment Video

Updated: Jul 23, 2025

Studying Mitotic Checkpoint by Illustrating Dynamic Kinetochore Protein Behavior and Chromosome Motion in Living Drosophila Syncytial Embryos
13:59

Studying Mitotic Checkpoint by Illustrating Dynamic Kinetochore Protein Behavior and Chromosome Motion in Living Drosophila Syncytial Embryos

Published on: June 14, 2012

11.4K

CAMK2D serves as a molecular scaffold for RNF8-MAD2 complex to induce mitotic checkpoint in glioma

You Heng Chuah1,2, Emmy Xue Yun Tay1,2, Oleg V Grinchuk1,2

  • 1Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117593, Singapore.

Cell Death and Differentiation
|July 19, 2023
PubMed

Insights

Researchers discovered a new CAMK2D-RNF8-MAD2 complex that regulates cell division. This complex

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The spindle assembly checkpoint (SAC) protein MAD2 is crucial for preventing mitotic progression by forming the mitotic checkpoint complex.
  • RNF8, a DNA damage response protein, has a poorly understood role in regulating the mitotic checkpoint.

Purpose of the Study:

  • To elucidate the precise role of RNF8 in mitotic checkpoint regulation.
  • To identify novel protein interactions and complexes involving RNF8 in cell cycle control.
  • To explore the therapeutic potential of targeting the identified complex in gliomas.

Main Methods:

  • Proximity proteomics to identify RNF8-interacting proteins.
  • Biochemical assays to characterize protein-protein interactions (RNF8-MAD2, CAMK2D-RNF8).
  • Functional assays in glioma stem cells (GSCs) to assess the impact of RNF8.
  • Chemical biology approaches to identify inhibitors targeting the pathway.

Main Results:

  • A novel CAMK2D-RNF8-MAD2 complex was identified, where RNF8 competes with p31comet for MAD2 binding and CAMK2D acts as a scaffold.
  • RNF8 overexpression impairs GSC mitotic progression in a manner dependent on its FHA and RING domains.
  • Low RNF8 expression correlates with poor glioma patient outcomes, and RNF8 overexpression reduces GSC tumorigenicity.
  • A PLK1 inhibitor mimics RNF8 overexpression effects; a PLK1/HSP90 inhibitor combination synergistically reduces GSC proliferation and stemness.

Conclusions:

  • The study reveals a novel CAMK2D-RNF8-MAD2 complex critical for generating the mitotic checkpoint signal.
  • This complex plays a significant role in regulating glioma stem cell proliferation and tumorigenicity.
  • The identified pathway represents a potential therapeutic target for glioma treatment.

More Related Videos

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis08:33

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

14.3K
Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene08:18

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene

Published on: December 31, 2014

28.1K

Related Concept Videos

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...
3.2K
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...
5.6K
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...
4.8K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.7K
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.
5.5K
The Cell Cycle Control System01:28

The Cell Cycle Control System

The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
3.1K