Anaphase-Promoting Complex (also called the cyclosome or APC/C) is an E3 ubiquitin ligase that marks target cell cycle proteins for degradation by the 26S proteasome. The APC/C's main function is to trigger the transition from metaphase to anaphase by tagging specific proteins for degradation. The three major targets for degradation by the APC/C are securin and S and M cyclins.
Composition of APC/C
APC/C is a multisubunit complex, and there are at least ten subunits in human cells and frog eggs, APC1 is the largest subunit of APC/C. The structural motifs of protein containing two large subunits Rpn1 and Rpn1 regulatory particle of non-AT-Pasein are identical to those of the 19s hat complex of proteasome, but the structural and functional significance of this similarity is not clear. APC2, a new member of the cullin protein family, is the only known APC/C subunit that can predict its function based on its protein sequence.
Function of APC/C
The results showed that the degradation of cyclin A and cyclin B was achieved by APC-C-dependent ubiquitin pathway. Treatment of Xenopus laevis extract with anti-APC/C antibody could result in the loss of Utopinylation activity of APC/C. It was found that the degradation of APC-C substrate late inhibitory factor initiated the cell transition from metaphase to anaphase. So far, two late inhibitory factors have been identified: Pds1 protein in budding yeast and Cut2 protein in merozoite yeast. Although the two proteins have no obvious homology in sequence, they exhibit similar functions and both contain a destruction frame sequence similar to M cycle protein. It is degraded by APC/C during the transition from mid to late stage. It was found that the degradation of substrates was in a certain order and performed different functions. First, Pds1/cut 2 was degraded, sister chromatid was separated and mitotic metaphase changed to anaphase. Then the M phase cyclin degrades and the cells withdraw from M phase to enter the next cell cycle. These findings suggest that APC-C-dependent proteins degrade and control spindle function in a more direct manner.
The activity Regulation of APC/C
It was found that the phosphorylation and dephosphorylation of APC/C regulated the activity of APC/C. Some of his subunits were not active when they were not phosphorylated. In phosphorylation, APC/C was active. PLK kinase was the positive regulator of APC/C. Phosphorylated APC/C enhances the ubiquitin activity of cyclin. The activity of APC/C is also regulated by the spindle assembly inspection point. Spindle assembly is incomplete and APC/C cannot be activated later on.
Abnormal function of APC/C promotes tumor Development
Protein degradation, especially the ubiquitin proteasome degradation system, is the key protein to regulate cell growth, proliferation and apoptosis. It plays a very important role in maintaining cell homeostasis. Its abnormality is closely related to tumorigenesis and development.
As mentioned earlier, APC/C plays an important regulatory role in the process of cell mitosis. If the system is maladjusted, it will result in the failure of the mitotic sister chromosomes to separate and the deletion of chromosomes. Both conditions can lead to chromosomal abnormalities and even tumorigenesis.