The Mad2-Binding Protein p31^comet as a Potential Target for Human Cancer Therapy

The spindle assembly checkpoint (SAC) is a surveillance mechanism that prevents mitotic exit at the metaphase-to-anaphase transition until all chromosomes have established correct bipolar attachment to spindle microtubules. Activation of SAC relies on the assembly of the mitotic checkpoint complex (MCC), which requires conformational change from inactive open Mad2 (OMad2) to the active closed Mad2 (C-Mad2) at unattached kinetochores. The Mad2-binding protein p31^comet plays a key role in controlling timely mitotic exit by promoting SAC silencing, through preventing Mad2 activation and promoting MCC disassembly. Besides, increasing evidences highlight the p31^comet potential as target for cancer therapy. Here, we provide an updated overview of the functional significance of p31^comet in mitotic progression, and discuss the potential of deregulated expression of p31^comet in cancer and in therapeutic strategies.