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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...
Anaphase A and B01:39

Anaphase A and B

Microtubules form through the end-to-end polymerization of tubulin heterodimers. Kinetochore microtubules originate from the spindle poles, and their plus-ends connect with the kinetochores on sister-chromatids. Ndc80 protein complexes, present on the kinetochore, form low-affinity links with the plus end of these kinetochore microtubules.
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
Anaphase A and B01:39

Anaphase A and B

Microtubules form through the end-to-end polymerization of tubulin heterodimers. Kinetochore microtubules originate from the spindle poles, and their plus-ends connect with the kinetochores on sister-chromatids. Ndc80 protein complexes, present on the kinetochore, form low-affinity links with the plus end of these kinetochore microtubules.
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
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...

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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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Identification of a physiological E2 module for the human anaphase-promoting complex.

Adam Williamson1, Katherine E Wickliffe, Barbara G Mellone

  • 1Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 14, 2009
PubMed
Summary

The anaphase-promoting complex (APC/C) requires Ube2S and UbcH10 for cell division. This E2 module is crucial for degrading mitotic regulators, ensuring proper spindle assembly and cell cycle progression.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The anaphase-promoting complex (APC/C) is a crucial ubiquitin ligase complex essential for cell proliferation.
  • APC/C orchestrates cell cycle progression by degrading key mitotic regulators.
  • The E2 enzyme UbcH10 initiates the formation of K11-linked ubiquitin chains catalyzed by human APC/C.

Purpose of the Study:

  • To identify and characterize novel E2 enzymes involved in APC/C-mediated ubiquitination.
  • To elucidate the role of Ube2S in APC/C activity and cell division.
  • To investigate the functional relationship between UbcH10 and Ube2S within the APC/C machinery.

Main Methods:

  • Identification of Ube2S as a K11-specific chain-elongating E2 enzyme for human and Drosophila APC/C.
  • Assessment of Ube2S activity dependence on APC/C activators Cdc20 and Cdh1.
  • Analysis of cellular phenotypes, including APC/C substrate stability, spindle defects, and mitotic delay, upon Ube2S depletion or loss of the UbcH10/Ube2S module.

Main Results:

  • Ube2S was identified as a conserved K11-specific chain-elongating E2 enzyme for APC/C in humans and Drosophila.
  • Ube2S activity is regulated by its cell cycle-dependent association with APC/C activators Cdc20 and Cdh1.
  • Depletion of Ube2S impaired APC/C function, while the loss of the UbcH10/Ube2S module caused severe stabilization of APC/C substrates, spindle defects, and mitotic delay.
  • Ube2S and UbcH10 are co-regulated through APC/C-dependent degradation during the cell cycle.

Conclusions:

  • UbcH10 and Ube2S form a physiological E2 module essential for APC/C function.
  • This E2 module's activity is critical for proper spindle assembly and successful cell division.
  • The coordinated regulation of UbcH10 and Ube2S ensures timely degradation of mitotic regulators, maintaining genomic stability.