Anaphase promoting complex: structure and expression

The anaphase promoting complex (APC) is the largest Cullin-RING E3 ligase that plays a critical role in cell cycle control and known as target of anti-cancer agents. APC regulates the onset of chromosome separation and mitotic exit via securin and cyclin B degradation, respectively. APC controls this process by mediating ubiquitin conjugation to substrates such as cyclin B and securin. The objective of this study was to evaluate the expression pattern of APC subunits in cancer cell lines and AML patients. Moreover, inhibitory compounds were designed based on the 3D structure of the APC and their inhibitory effects were investigated on HeLa and MDA-MB-435 cell lines. To do this, the 3D structure of APC was predicted using homology modelling and molecular dynamic simulation. Interaction among APC subunits were studied by using protein-protein docking methods. It was found that catalytic subunits of APC over-expressed in cancer cell lines and AML patients. Furthermore, the APC subunits assembly and activation was demonstrated at the atomic-level.