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Related Concept Videos

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...
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...
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...
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.
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
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...

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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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How APC/C-Cdc20 changes its substrate specificity in mitosis.

Daisuke Izawa1, Jonathon Pines

  • 1Gurdon Institute and Department of Zoology, Tennis Court Road,Cambridge CB2 1QN, UK.

Nature Cell Biology
|February 22, 2011
PubMed
Summary
This summary is machine-generated.

The spindle assembly checkpoint (SAC) alters how Cdc20 binds to the anaphase-promoting complex/cyclosome (APC/C). This mechanism controls the degradation of key mitotic proteins, ensuring proper cell division.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitotic progression relies on precise protein degradation.
  • The anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase regulates key mitotic proteins.
  • The spindle assembly checkpoint (SAC) modulates APC/C activity via Cdc20.

Purpose of the Study:

  • To elucidate the mechanism by which the SAC influences APC/C substrate specificity.
  • To understand how Cdc20 binding to the APC/C is regulated by the SAC.

Main Methods:

  • Investigated the interactions between Cdc20, the APC/C, and its subunits (APC3, APC8, APC10) under different SAC conditions.
  • Assessed the role of specific APC/C subunits in substrate degradation.

Main Results:

  • Cdc20 binding sites on the APC/C differ depending on SAC activity.
  • SAC satisfaction requires APC3 and APC8 for Cdc20 binding; active SAC requires only APC8.
  • APC10 is essential for cyclin B1 and securin degradation but not cyclin A degradation.

Conclusions:

  • The SAC induces differential binding of Cdc20 to the APC/C.
  • Altered Cdc20-APC/C interactions mediate changes in APC/C substrate specificity during mitosis.
  • This provides a molecular basis for selective protein degradation during the cell cycle.