APC/C coactivators Cdh1 and Cdc20: Mechanistic insights into cancer progression and therapeutic opportunities.

The dysregulation of the cell cycle is intricately linked to the pathogenesis and progression of numerous human diseases, especially for malignant tumors. The anaphase-promoting complex/cyclosome (APC/C), an evolutionarily conserved protein complex, plays a pivotal role in regulating the metaphase-to-anaphase transition during mitosis, making it indispensable for cellular division. APC/C requires binding to co-activators Cdh1 (also known as Fizzy-related protein 1, Cdh1) and Cdc20 (cell division cycle 20 homolog, also called Fizzy) to form the enzymatically active APC/CCdh1 and APC/CCdc20 complexes.This review provides a comprehensive synthesis of recent advancements in deciphering the multifaceted roles of APC/C coactivators Cdh1 and Cdc20 in cancer initiation, progression, and therapeutic. We first outline the structural architecture and functional mechanisms of APC/C, then dissect the distinct patterns of dysregulation exhibited by Cdh1 and Cdc20 in human malignancies. Additionally, we discuss current developments in APC/C-targeting inhibitors, explore innovative therapeutic strategies leveraging APC/C modulation, and identify emerging frontiers for future research.