APCCcomplex

APCC complex, also known as the Anaphase-Promoting Complex/Cyclosome, is a multi-subunit ubiquitin ligase that plays a critical role in cell cycle progression, particularly during mitosis. Its primary function is to target specific proteins for degradation by the 26S proteasome, thereby driving key transitions in the cell cycle.

The APCC complex is composed of approximately 15 different subunits, many of which are homologous to yeast proteins. It functions as a key regulator of the metaphase-to-anaphase transition. During this critical stage, the APCC ubiquitinates and targets for destruction proteins such as securin and cyclin B. The degradation of securin, which inhibits the enzyme separase, allows separase to cleave cohesin, the protein complex that holds sister chromatids together. This cleavage enables sister chromatids to separate and move to opposite poles of the cell, initiating anaphase. The destruction of cyclin B, a component of cyclin-dependent kinases (CDKs), leads to the inactivation of these kinases, which are necessary for maintaining the mitotic state.

The activity of the APCC complex is tightly regulated by other proteins, most notably the spindle assembly checkpoint (SAC). The SAC monitors chromosome attachment to the spindle and prevents premature activation of the APCC until all chromosomes are properly aligned. Other regulatory proteins, such as Cdc20 and Cdh1, act as co-activators, binding to the APCC and directing it to its specific substrates. The choice of co-activator influences the APCC's substrate specificity and timing of activation, contributing to the ordered progression of the cell cycle. Dysregulation of APCC function can lead to aneuploidy and has been implicated in cancer development.