anaphase-promoting complex-dependent catabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, with ubiquitin-protein ligation catalyzed by the anaphase-promoting complex, and mediated by the proteasome. [GOC:mah, PMID:15380083, PMID:15840442]

The anaphase-promoting complex-dependent catabolic process is a tightly regulated cellular mechanism that plays a crucial role in the progression of the cell cycle, particularly during the transition from metaphase to anaphase. This process involves the targeted degradation of specific proteins via the ubiquitin proteasome system, facilitated by the anaphase-promoting complex/cyclosome (APC/C). The APC/C is a multi-subunit E3 ubiquitin ligase, a complex molecular machine responsible for tagging proteins with ubiquitin chains, marking them for destruction by the proteasome.

The APC/C acts as a molecular switch, transitioning between two distinct active states, each characterized by its specific regulatory subunits and target protein repertoire. During metaphase, the APC/C associates with the protein Cdc20. This complex targets proteins involved in sister chromatid cohesion, such as securin and cyclin B. Securin inhibits separase, an enzyme responsible for cleaving the proteins holding sister chromatids together, while cyclin B is a key component of the M-phase promoting factor (MPF), a protein complex that drives entry into mitosis. Degradation of these proteins by the APC/C/Cdc20 complex allows for the separation of sister chromatids and the initiation of anaphase.

As the cell progresses into anaphase and the chromosomes are pulled to opposite poles, the APC/C transitions to its second active state. It now associates with the protein Cdh1, shifting its target protein specificity. This shift in substrate recognition enables the APC/C/Cdh1 complex to target a broader range of proteins, including mitotic cyclins, cell cycle regulators, and components of the mitotic spindle. The degradation of these proteins ensures the proper completion of mitosis, the inactivation of the mitotic program, and the transition into the next cell cycle phase, G1.

The regulation of the APC/C/Cdh1 complex during anaphase and G1 is crucial for maintaining genomic integrity and preventing premature entry into mitosis. Its activity is tightly controlled by phosphorylation, protein interactions, and the availability of its substrates. Defects in the anaphase-promoting complex-dependent catabolic process can lead to various cellular dysfunctions, including aneuploidy, cell cycle arrest, and uncontrolled cell proliferation, contributing to various diseases, including cancer.'
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Proteins (1)

Compounds (1)