Anaphase-promoting complex

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Anaphase-promoting complex

Anaphase-Promoting Complex (APC), also known as the Cyclosome, is a crucial multi-subunit E3 ubiquitin ligase that regulates the cell cycle by triggering the onset of anaphase and ensuring the exit from mitosis. It marks specific cell cycle proteins for degradation by the 26S proteasome, thereby controlling cell cycle progression. The APC is highly conserved across eukaryotes, underscoring its essential role in cell biology.

Function

The primary function of the Anaphase-Promoting Complex is to initiate anaphase by targeting securin, an inhibitor of separase, for degradation. This degradation allows separase to cleave cohesin, the protein complex that holds sister chromatids together, thereby enabling their separation to opposite poles of the cell. Additionally, APC regulates the exit from mitosis by targeting cyclin B, a component of the Cdk1 complex, marking it for degradation and leading to the deactivation of Cdk1, thus promoting exit from mitosis and entry into the G1 phase of the cell cycle.

Components

The Anaphase-Promoting Complex is a large complex that consists of at least 12 core subunits, including APC1, APC2, APC4, APC5, and the cullin domain-containing APC2 and RING-H2 domain-containing APC11, which are critical for its ubiquitin ligase activity. The activity of the APC is regulated by two co-activators, Cdc20 and Cdh1, which bind to the APC at different stages of the cell cycle, directing its specificity towards different substrates.

Regulation

The activity of the APC is tightly regulated throughout the cell cycle. During metaphase, the Mitotic checkpoint complex (MCC) inhibits APC^Cdc20, preventing premature separation of sister chromatids. Once all chromosomes are properly attached to the mitotic spindle and aligned at the metaphase plate, the MCC is inactivated, allowing APC^Cdc20 to initiate anaphase. Following anaphase onset, APC^Cdh1 becomes active, targeting not only mitotic cyclins but also other proteins to ensure exit from mitosis and maintenance of the G1 phase.

Clinical Significance

Dysregulation of the Anaphase-Promoting Complex has been implicated in various cancers, as it can lead to genomic instability and uncontrolled cell proliferation. Inhibitors of the APC are being explored as potential therapeutic agents for cancer treatment.

See Also

• Cell cycle
• Ubiquitin-proteasome system
• Mitosis
• Cyclin-dependent kinase