Implications

The  full mechanism for MCC-mediated inhibition is unknown but there are theories about the mechanisms involved in it.

MCC-mediated inhibition of APC/C

Mad3 blocks protometaphase and metaphase substrate recognition of APC/C using Cdc20^[1] .This assumption is supported by the fact that the KEN box blocks the binding site and stimulates the degradation of Cdc20 by binding to Cdc20 through its KEN-box recognition site. It is suggested that Mad 3 is potentially involved the ubiquitination of Cdc20 using APC/C’s catalytic site. Also, the lowering of the position of Cdc20 by binding to Mad2 prevents the D-box binding site from forming a complex with co-receptors in APC/C.

The removal of Cdc20’s N-terminal by Mad2 is suggested to influence the positioning and functional activity of Cdc20^[1]. By removing the N-terminal, this could prevent the C-box from binding to the APC/C binding site; subsequently, APC/C catalytic activity is inhibited. 

Disease implications
If co-activators, Cdc20 and Cdh1 aren’t present in the cell, cells aren’t able to complete the cell cycle, leading cells to undergo cell cycle arrest. This is heavily linked to cancer as genomic instability occurs.

p31comet is capable of interfering with MCC-mediated inhibition of APC/C. Therefore, the reduction in MCC's activity can lead to genetic instability, such as aneuploidy which is associated with tumorigenesis.^[2] An example of this has been seen with heterozygous mice containing a faulty Mad2 protein developing benign lung cancer spontanteously due to their increased chemical sensitivity through lose of function from Mad2.^[2] However, this correlation doesn't mean aneuploidy causes cancer as the mitotic checkpoint proteins also participate in other roles within the cell and further research needs to be done.