Human ANAPC15 is a component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. In the complex, it plays a role in the release of the mitotic checkpoint complex (MCC) from the APC/C; it is not required for APC/C activity itself, but promotes the turnover of CDC20 and MCC on the APC/C, thereby participating to the responsiveness of the spindle assembly checkpoint. It also required for degradation of CDC20 [].
Mad2 is a central component of the spindle assembly checkpoint, which is a feedback control that prevents cells with incompletely assembled spindles from leaving mitosis [, ]. In Saccharomyces cerevisiae, it is a component of the mitotic checkpoint complex (MCC) which consists of MAD2, MAD3, BUB3 and CDC20, and of the MAD2-CDC20 subcomplex, both of which appear to be assembled during mitoisis independently of the kinetochore. MCC and presumably the MAD2-CDC20 subcomplex inhibit the ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) by preventing its activation by CDC20 [, , ].
This entry includes Harmonin-binding protein USHBP1 also known as MCC2) and colorectal mutant cancer protein known as MCC. MCC has been found to suppresses cell proliferation and the Wnt/b-catenin pathway in colorectal cancer cells [, ]. It may works as a scaffold protein regulating cell movement and able to bind Scrib, beta-catenin and NHERF1/2 []. MCC1 inhibits DNA binding of b-catenin/TCF/LEF transcription factors, and it is involved in cell migration independently of RAC1, CDC42 and p21-activated kinase (PAK) activation [, , ].MCC2 protein binds the first PDZ domain of AIE-75 with its C-terminal amino acids -DTFL. A possible role of MCC2 as a tumour suppressor has been put forward. The carboxyl terminus of the predicted protein was DTFL which matched the consensus motif X-S/T-X-phi (phi: hydrophobic amino acid residue) for binding to the PDZ domain of AIE-75 [, ].
