mitotic checkpoint complex

Definition

Target type: cellularcomponent

A multiprotein complex that functions as a mitotic checkpoint inhibitor of the anaphase-promoting complex/cyclosome (APC/C). In budding yeast this complex consists of Mad2p, Mad3p, Bub3p and Cdc20p, and in mammalian cells it consists of MAD2, BUBR1, BUB3, and CDC20. [PMID:10704439, PMID:11535616, PMID:11726501, PMID:17650307]

The mitotic checkpoint complex (MCC) is a multi-protein complex that ensures proper chromosome segregation during cell division. It functions as a critical regulator of the metaphase-to-anaphase transition, preventing premature separation of sister chromatids until all chromosomes are properly aligned at the metaphase plate. The MCC is localized to kinetochores, specialized protein structures that assemble on centromeres of chromosomes. It is composed of several key proteins, including:

* **BubR1 (BUB1 related 1)**: This protein acts as a sensor for proper kinetochore-microtubule attachment. It interacts with the microtubule-binding protein Mad2 and helps recruit it to unattached kinetochores.
* **Mad2 (mitotic arrest deficient 2)**: This protein is a key component of the MCC and plays a central role in inhibiting the anaphase promoting complex/cyclosome (APC/C), the ubiquitin ligase responsible for initiating anaphase. Mad2 exists in two conformations: an open conformation that can bind to Mad1 and a closed conformation that binds to Cdc20, a co-activator of APC/C.
* **Bub3 (BUB1 related 3)**: This protein associates with BubR1 and Mad2, forming a complex that interacts with the spindle assembly checkpoint protein Mad1.
* **Cdc20 (cell division cycle protein 20)**: This protein is a co-activator of APC/C and is normally inhibited by the MCC. When all chromosomes are properly attached to microtubules, the MCC disassembles, releasing Cdc20 to activate APC/C, initiating anaphase.

The MCC functions as a "wait-anaphase" signal, ensuring that the cell does not progress into anaphase until all chromosomes are properly aligned at the metaphase plate. When a chromosome is not properly attached to microtubules, the MCC is assembled at the kinetochore, preventing Cdc20 from activating APC/C and blocking entry into anaphase. Once all chromosomes are properly attached, the MCC disassembles, allowing Cdc20 to activate APC/C and initiating anaphase. This complex mechanism ensures accurate chromosome segregation during mitosis, preventing aneuploidy and maintaining genome integrity.'
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Proteins (1)

Compounds (1)