APC/C: current understanding and future perspectives.

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The anaphase-promoting complex/cyclosome (APC/C) is a crucial E3 ubiquitin ligase regulating the cell cycle.
• APC/C controls the irrevocable separation of sister chromatids during anaphase.
• Key regulators like APC/C and cyclin-dependent kinase 1 (Cdk1) utilize ubiquitylation and phosphorylation, respectively.

Purpose of the Study:

• To review the historical background and current understanding of APC/C regulation.
• To explore the multifaceted mechanisms governing APC/C's temporal and spatial control.
• To highlight recent advancements in understanding APC/C's molecular mechanisms.

Main Methods:

• Review of existing literature on APC/C.
• Analysis of high-resolution cryogenic electron microscopy (cryo-EM) data.
• Examination of APC/C reconstitution studies.

Main Results:

• APC/C regulation involves phosphorylation, co-activators (Cdc20, Cdh1), E2 enzymes, inhibitors, and substrate affinities.
• Despite extensive research, a complete understanding of APC/C remains elusive.
• Recent cryo-EM and reconstitution studies provide molecular insights into APC/C's enzymatic functions.

Conclusions:

• The regulation of APC/C is complex and involves numerous interacting factors.
• Continued research, particularly using advanced structural biology techniques, is vital for fully elucidating APC/C function.
• Understanding APC/C is critical for comprehending cell cycle control and its dysregulation in diseases.