PathwayStep4496 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal Amplification of signal from the kinetochores A single unattached kinetochore is capable of preventing cells from exiting mitosis. The mitotic checkpoint provides a way for a localized defect to affect the global biochemical status of the cell. In principle, the signal that is generated at an unattached kinetochore diffuses throughout the cell to affect its target. There are currently two models for how this is achieved. One model is based on the observation that the Mad2 checkpoint protein binds and is rapidly released from unattached kinetochores. The kinetochore is believed to act as a catalyst that converts Mad2 into an inhibitory state that diffuses throughout the cell upon its release from the kinetochore. A second model proposes that the signal is amplified by a kinase cascade much like a conventional signal transduction pathway. This kinase cascade is believed to be comprised of the checkpoint kinases, hBUBR1, hBUB1, hMPS1. Authored: Yen, T, 2004-05-05 00:00:00 Pubmed14593737 Reactome Database ID Release 43141424 Reactome, http://www.reactome.org ReactomeREACT_795