18.18: 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 activates it, resulting in the formation of APC^Cdc20 and APC^Cdh1 complexes, respectively. Cdc20 and Cdh1 also help APC to identify its substrates.

APC^Cdc20 plays an essential role in metaphase to anaphase transition. The sister chromatids are held together by cohesins. The cohesin rings need to be broken by the enzyme separase so that the sister chromatids can move towards the opposite poles during anaphase. However, separase activity is inhibited by the protein, securin. APC^Cdc20 ubiquitinates securin, leading to its proteasomal degradation. This leads to the subsequent activation of the separase. APC^Cdc20 also ubiquitinates mitotic cyclins, which in turn inactivates cyclin-dependent kinases or Cdks. The inactivation of Cdks and the subsequent dephosphorylation of Cdk-substrates are necessary for the completion of cell division.

The successful completion of anaphase also depends on the activity of a ubiquitin ligase called anaphase-promoting complex or cyclosome APC/C.

During the transition to anaphase, the protein Cdc20 binds to and activates APC/C. The activated APC/C ubiquitinates the regulatory proteins, S-cyclins and M-cyclins, thereby targeting them for proteasomal degradation.

Cyclin degradation inhibits the activity of most Cdks. The absence of cyclin-dependent kinase activity enables phosphatases to dephosphorylate most of the Cdk-substrates within the cell, which is required for the completion of anaphase.

• Anaphase - Crucial phase in cell division, with the separation of paired chromosomes.
• Cell Cycle - The process of cell duplication, from origin to division.
• SCF (Skp1/Cullin/F-box) - A type of ubiquitin ligase involved in cell cycle progression.
• Anaphase-Promoting Complex (APC) - A ubiquitin ligase that triggers anaphase and cyclin degradation.
• Cdc20 and Cdh1 - Proteins that bind and activate APC, helping to identify substrates.

• Define Anaphase – Understand the role of it in cell division (e.g., anaphase).
• Contrast SCF vs APC – Learn their different functionalities in the cell cycle (e.g., SCF and APC).
• Explore Cdc20 and Cdh1 – Discover how they activate APC (e.g., Cdc20 and Cdh1).
• Explain Ubiquitination – Learn how it leads to the destruction of proteins.
• Apply in Cell Cycle Context – Understand how these proteins regulate the cell division process.

• What is the function of anaphase in the cell cycle?
• How does the APC complex contribute to cell cycle progression?
• What role do Cdc20 and Cdh1 play in activating APC?

• Biology Students – Understand how ubiquitin ligases like SCF and APC support cell cycle progression
• Cell-Biology Educators – Provides a clear framework for teaching cell cycle regulation.
• Cell Biology Researchers – Understand the role of ubiquitination in cell-cycle regulation
• Science Enthusiasts – Offer insights into the complexities of cell division and cell cycle regulation