ANAPC - Anaphase-promoting complex subunit | Elisa - Clia - Antibody - Protein

Background:

ANAPC, or Anaphase-Promoting Complex, is a multi-subunit protein complex that plays a crucial role in regulating the cell cycle, particularly in the transition from metaphase to anaphase during mitosis and meiosis. It is also known as the APC/C (Anaphase-Promoting Complex/Cyclosome). ANAPC is an E3 ubiquitin ligase, meaning it tags specific proteins for degradation by the proteasome through the addition of ubiquitin molecules. Its primary function is to target key cell cycle regulators for degradation, allowing the cell cycle to progress in a coordinated and controlled manner. ANAPC regulates the transition from metaphase to anaphase by targeting proteins such as securin and cyclin B for degradation. NAPC is composed of multiple subunits, each with specific roles in the complex's function.The core of the ANAPC consists of at least 13 subunits, including ANAPC1 through ANAPC13. These subunits come together to form a complex with a highly organized structure. ANAPC1 (also known as APC1) serves as the scaffold for the entire complex, providing a platform for the other subunits to assemble. ANAPC2 (APC2) and ANAPC11 (APC11) are responsible for the catalytic activity of the E3 ubiquitin ligase. ANAPC3 (APC3) and ANAPC8 (APC8) are involved in substrate recognition and binding. Other subunits, such as ANAPC4 (APC4), ANAPC5 (APC5), ANAPC6 (APC6), ANAPC7 (APC7), and ANAPC10 (APC10), contribute to the stability and regulation of the complex.

Protein Structure:

• Core Complex: The APC/C is a large multi-protein complex comprising at least 13 core subunits, including ANAPC1, ANAPC2, ANAPC4, ANAPC5, ANAPC6, ANAPC7, ANAPC10, ANAPC11, and others.
• Catalytic Subunits: ANAPC2 and ANAPC11 are key catalytic components responsible for the ubiquitin ligase activity of the complex.
• Adaptor and Scaffold Subunits: Other subunits, such as ANAPC1, ANAPC4, and ANAPC5, function as scaffolds and adaptors, helping to organize the complex and recruit substrates and co-activators.
• Structure: The APC/C has a complex three-dimensional structure, characterized by a central catalytic core surrounded by multiple regulatory and scaffold subunits. This arrangement allows for the precise regulation of its ubiquitin ligase activity.

Classification and Subtypes:

• Subunits: The ANAPC subunits are individually named (e.g., ANAPC1, ANAPC2, ANAPC4, etc.), each contributing specific functions to the overall complex.
• Functional Modules: The APC/C can be divided into functional modules based on the roles of its subunits, such as the catalytic module, substrate recognition module, and regulatory module.

Function and Biological Significance:

• Cell Cycle Regulation: The primary function of the APC/C is to regulate the cell cycle by targeting cell cycle proteins, such as cyclins and securin, for degradation. This ensures the proper timing of cell cycle transitions, particularly the exit from mitosis.
• Ubiquitination: The APC/C mediates the ubiquitination of its substrates, marking them for destruction by the 26S proteasome. This process is essential for the separation of sister chromatids during anaphase and the exit from mitosis.
• Checkpoint Control: The APC/C is tightly regulated by the spindle assembly checkpoint (SAC) to prevent premature separation of chromosomes. Co-activators like Cdc20 and Cdh1 are essential for its activation at specific cell cycle stages.

Interactions:

• Substrate Interaction: The APC/C interacts with various cell cycle proteins, targeting them for ubiquitination and degradation.
• Regulatory Proteins: It interacts with regulatory proteins such as Cdc20 and Cdh1, which activate the complex at different stages of the cell cycle.
• Checkpoint Proteins: The spindle assembly checkpoint proteins (e.g., Mad2, BubR1) interact with the APC/C to inhibit its activity until all chromosomes are properly aligned.

Clinical Issues:

• Cancer: Dysregulation of the APC/C can lead to uncontrolled cell division and aneuploidy, contributing to tumorigenesis. Mutations or aberrant expression of APC/C subunits or regulators are implicated in various cancers.
• Therapeutic Targets: Components of the APC/C are potential targets for cancer therapy. Inhibitors of the APC/C or its regulatory proteins can be used to induce cell cycle arrest and apoptosis in cancer cells.

Summary:

The Anaphase-Promoting Complex (APC/C) is a crucial E3 ubiquitin ligase involved in regulating the cell cycle by targeting key proteins for degradation. Composed of multiple subunits, including ANAPC1, ANAPC2, and others, it ensures the proper progression from metaphase to anaphase and the exit from mitosis. The APC/C interacts with various regulatory and checkpoint proteins to maintain genomic stability. Dysregulation of the APC/C is associated with cancer, making it a significant target for therapeutic intervention. Understanding the structure, function, and regulation of the APC/C is essential for developing strategies to modulate its activity in disease contexts.