Mitosis: Cdh1 clears the way for anaphase spindle assembly
1Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Department of Oncology, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK. Fanni.Gergely@cancer.org.uk
Current Biology : CB
|November 13, 2008
Summary
The anaphase-promoting complex/cyclosome (APC/C) co-activators Cdc20 and Cdh1 control substrate specificity. Cdc20-APC/C degrades most Cdh1 targets, but not Aurora kinases, leading to cell division errors.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The anaphase-promoting complex/cyclosome (APC/C) is a crucial ubiquitin ligase regulating cell cycle progression.
- Cdc20 and Cdh1 are key co-activators that confer substrate specificity to the APC/C.
- The precise roles of Cdc20 and Cdh1 in substrate selection and degradation remain incompletely understood.
Purpose of the Study:
- To investigate the substrate specificity of Cdc20-bound APC/C compared to Cdh1-bound APC/C.
- To determine the impact of differential substrate degradation on cell division processes.
Main Methods:
- Utilized biochemical assays to analyze APC/C activity with Cdc20 and Cdh1 co-activators.
- Performed proteolysis assays to identify APC/C substrates.
- Investigated the consequences of altered Aurora kinase levels on anaphase and cytokinesis.
Main Results:
- Cdc20-bound APC/C mediates the timely degradation of numerous Cdh1 substrates.
- Aurora kinases were identified as exceptions, not being degraded by Cdc20-APC/C.
- Failure to degrade Aurora kinases resulted in aberrant anaphase microtubule organization and premature cytokinesis.
Conclusions:
- Cdc20-APC/C exhibits distinct substrate specificity, differing from Cdh1-APC/C.
- Differential degradation of substrates, particularly Aurora kinases, by APC/C co-activators is critical for accurate cell division.
- Dysregulation of Aurora kinase degradation by APC/C leads to severe defects in cell division.
Related Concept Videos
02:17Separation 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...
At the onset of anaphase, separase, a proteolytic enzyme, is...
02:17Separation 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...
At the onset of anaphase, separase, a proteolytic enzyme, is...
02:19The 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...
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...
02:19The 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...
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...
02:15M-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...
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...
02:15M-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...
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...