Structure, function and mechanism of the anaphase promoting complex (APC/C).

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• The cell cycle involves complex molecular events coordinating replication, segregation, division, and growth.
• Protein degradation, primarily via the ubiquitin proteasome system, is key to cell cycle control.
• The anaphase promoting complex (APC/C) is a critical E3 ubiquitin ligase regulating mitosis and S phase entry.

Purpose of the Study:

• To discuss the anaphase promoting complex (APC/C) from structural and mechanistic viewpoints.
• To provide insights into the molecular mechanisms of APC/C catalysis, substrate recognition, and structural organization.

Main Methods:

• Genetic studies
• Biochemical analyses
• Electron microscopy of intact APC/C
• Crystallographic analysis of individual subunits
• Analogies to related RING family E3 ligases

Main Results:

• The APC/C targets proteins like cyclins via destruction motifs (D-box, KEN-box).
• APC/C activity and substrate specificity are temporally regulated by co-activators, phosphorylation, and inhibitors.
• Insights into APC/C's molecular mechanisms and structure have been gained despite the lack of a complete atomic structure.

Conclusions:

• The APC/C plays a vital role in cell cycle progression through regulated protein ubiquitylation.
• Understanding APC/C structure and mechanism is essential for comprehending cell cycle control.
• Further structural studies will enhance our knowledge of this critical E3 ligase.