anaphase-promoting complex

Definition

Target type: cellularcomponent

A ubiquitin ligase complex that degrades mitotic cyclins and anaphase inhibitory protein, thereby triggering sister chromatid separation and exit from mitosis. Substrate recognition by APC occurs through degradation signals, the most common of which is termed the Dbox degradation motif, originally discovered in cyclin B. [GOC:jh, GOC:vw, PMID:10465783, PMID:10611969]

The anaphase-promoting complex (APC/C) is a multi-subunit E3 ubiquitin ligase that plays a crucial role in cell cycle regulation, particularly during the transition from metaphase to anaphase and the exit from mitosis. It is composed of a core complex of 13 subunits, namely:

**Core Subunits:**

- **APC1:** A large scaffolding protein that forms the core structure of the APC/C.
- **APC2:** Another scaffolding protein essential for the assembly and activity of the APC/C.
- **APC3:** This subunit plays a crucial role in the recognition and binding of substrates.
- **APC4:** A subunit important for the ubiquitination activity of the APC/C.
- **APC5:** A subunit that contributes to the stability and function of the APC/C.
- **APC6:** This subunit helps in the recruitment and activation of the E2 ubiquitin conjugating enzyme.
- **APC7:** A subunit important for the structural integrity of the APC/C.
- **APC8:** This subunit contributes to the overall assembly and activity of the APC/C.
- **APC10:** A subunit that interacts with other components and influences substrate recognition.
- **APC11:** A subunit that participates in the regulation of the APC/C activity.
- **APC12:** This subunit plays a role in the interaction with the coactivator CDC20.
- **APC13:** A subunit important for the stability and function of the APC/C.
- **APC16:** A subunit that contributes to the overall activity of the APC/C.

**Coactivators:**

The APC/C requires coactivators, also known as activating subunits, for its full functionality. These coactivators are responsible for recognizing specific substrates and promoting their ubiquitination. The two main coactivators are:

- **CDC20:** This coactivator is essential for the initiation of anaphase and promotes the degradation of securin and cyclin B.
- **CDH1:** This coactivator is active during G1 and S phases and promotes the degradation of other substrates involved in cell cycle progression.

**Mechanism of Action:**

The APC/C, along with its coactivators, recognizes and binds to specific target proteins. This interaction triggers the ubiquitination of the target protein, leading to its degradation by the proteasome. The degradation of key regulatory proteins by the APC/C is essential for the proper progression of the cell cycle. For example, the degradation of securin allows the separation of sister chromatids during anaphase, while the degradation of cyclin B contributes to the exit from mitosis.

**Regulation:**

The activity of the APC/C is tightly regulated throughout the cell cycle. This regulation involves various mechanisms, including:

- **Phosphorylation:** The phosphorylation status of APC/C subunits can influence its activity.
- **Coactivator binding:** The binding of different coactivators (CDC20 and CDH1) determines which substrates will be recognized and degraded.
- **Post-translational modifications:** Other modifications, such as acetylation and sumoylation, can also affect the activity of the APC/C.

**Clinical Significance:**

Defects in the APC/C or its coactivators can lead to various diseases, including:

- **Cancer:** The APC/C is involved in the regulation of cell proliferation and apoptosis, and its dysregulation can contribute to uncontrolled cell growth and tumor development.
- **Neurological disorders:** The APC/C is also implicated in neuronal development and function, and mutations in its components can lead to developmental defects and neurodegenerative diseases.

**Overall, the anaphase-promoting complex (APC/C) is a crucial cellular machine that regulates cell cycle progression and prevents uncontrolled cell division. Its complex structure and intricate regulatory mechanisms highlight the importance of precise protein degradation in maintaining cellular homeostasis.'
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Proteins (1)

Compounds (1)