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APC/C coactivators Cdh1 and Cdc20: Mechanistic insights into cancer progression and therapeutic opportunities
Yaqi Zhang1, Haoyi Wang2, Kaifan Li2
1School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, Henan Province, China; Xinxiang Key Laboratory for Molecular Oncology, Institutes of Health Central Plains, Henan Medical University, Xinxiang 453003, Henan Province, China; School of Medical and Health Care, Qufu Fareast Vocational and Technical College, Jining 273100, Shangdong Province, China.
Abstract:
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.
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