7.18
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 ub…
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.
View the full transcript and gain access to JoVE Core videos
Q1: What is the anaphase-promoting complex and what does it do?
The anaphase-promoting complex, also called cyclosome or APC/C, is a ubiquitin ligase that regulates cell cycle progression by targeting specific proteins for destruction. During the metaphase to anaphase transition, APC/C becomes activated and ubiquitinates regulatory proteins, marking them for proteasomal degradation. This protein destruction is essential for completing anaphase and advancing cell division.
Q2: How does Cdc20 activate the anaphase-promoting complex?
Cdc20 is a regulatory protein that binds to and activates APC/C during the transition to anaphase. Once bound, Cdc20 helps APC/C recognize its target substrates and facilitates ubiquitination of mitotic cyclins and securin. This activation of APCCdc20 is critical for initiating the molecular events that allow sister chromatids to separate and anaphase to progress.
Q3: Why does APC/C target mitotic cyclins for degradation?
APC/C ubiquitinates mitotic cyclins, including S-cyclins and M-cyclins, to inactivate cyclin-dependent kinases or Cdks. When cyclin levels drop, Cdk activity ceases, allowing phosphatases to dephosphorylate Cdk-substrates throughout the cell. This dephosphorylation is necessary for completing anaphase and enabling the cell to exit mitosis.
Q4: What role does securin play in sister chromatid separation?
Securin inhibits the enzyme separase, which normally cleaves cohesin rings that hold sister chromatids together. APCCdc20 ubiquitinates securin, leading to its proteasomal degradation and subsequent activation of separase. Once separase is active, it breaks cohesin rings, allowing sister chromatids to move toward opposite poles during anaphase.
Q5: How does proteasomal degradation support anaphase completion?
Stepwise destruction of specific proteins by the proteasome is necessary for cell cycle progression. APC/C ubiquitinates target proteins like cyclins and securin, marking them for proteasomal degradation. This controlled protein destruction removes inhibitory signals, activates essential enzymes like separase, and inactivates Cdks, collectively enabling anaphase to complete successfully.
Q6: What happens to Cdk activity when cyclins are degraded?
Cyclin degradation by APC/C eliminates the regulatory subunits required for Cdk activation, causing Cdk activity to drop dramatically. Without active Cdks, phosphatases can dephosphorylate Cdk-substrates throughout the cell. This dephosphorylation reverses the phosphorylation events that maintained mitotic structures, allowing the cell to complete anaphase and progress toward cytokinesis.
Q7: How do APCCdc20 and APCCdh1 differ in their roles during cell division?
APCCdc20 is activated during metaphase to anaphase transition and targets securin and mitotic cyclins for degradation, enabling sister chromatid separation and Cdk inactivation. APCCdh1 becomes active later in mitosis and G1 phase, continuing cyclin degradation to maintain low Cdk activity. Both complexes use different co-activators to recognize substrates at different cell cycle stages.