CDC20

CDC20 (Cell Division Cycle 20) is a regulatory protein that plays a critical role in the mitotic checkpoint, which ensures proper cell division. It is a key activator of the anaphase-promoting complex (APC/C), a E3 ubiquitin ligase that marks target proteins for degradation, thereby controlling progression through mitosis. CDC20 has been implicated in various cellular processes including chromosome segregation, checkpoint control, and apoptotic signaling.

Function

CDC20 functions by binding to the APC/C, facilitating the ubiquitination and subsequent degradation of key cell cycle regulators such as securin and cyclin B. This degradation is essential for the transition from metaphase to anaphase, allowing for the separation of sister chromatids and the successful completion of cell division. CDC20's activity is tightly regulated by the spindle assembly checkpoint (SAC), a surveillance mechanism that delays anaphase onset until all chromosomes are properly attached to the mitotic spindle.

Regulation

The activity of CDC20 is regulated by several mechanisms. During the early stages of mitosis, CDC20 is inhibited by the SAC through direct binding of checkpoint proteins, such as Mad2, BubR1, and Bub3, which prevents premature activation of the APC/C. Once all chromosomes are correctly attached to the spindle, these inhibitory complexes disassemble, allowing CDC20 to activate the APC/C. Additionally, CDC20 itself is subject to ubiquitination and degradation, adding another layer of control over its activity.

Clinical Significance

Aberrant expression or malfunction of CDC20 has been linked to tumorigenesis and cancer progression. Overexpression of CDC20 has been observed in various types of cancer, where it may contribute to chromosomal instability and resistance to apoptosis. As such, CDC20 is considered a potential target for cancer therapy, with research focused on developing inhibitors that can selectively block its interaction with the APC/C.

Research

Research into CDC20 continues to uncover its complex role in cell cycle regulation and its potential implications for cancer therapy. Studies are exploring the detailed mechanisms of its regulation, interaction with the APC/C, and its role in the SAC. Understanding the precise functions and regulation of CDC20 is crucial for developing targeted therapies that could inhibit its activity in cancer cells without affecting normal cell division.