TY - JOUR TI - Protein Phosphatase 1 inactivates Mps1 to ensure efficient Spindle Assembly Checkpoint silencing AU - Moura, Margarida AU - Osswald, Mariana AU - Leça, Nelson AU - Barbosa, João AU - Pereira, António J AU - Maiato, Helder AU - Sunkel, Claudio E AU - Conde, Carlos A2 - Musacchio, Andrea VL - 6 PY - 2017 DA - 2017/05/02 SP - e25366 C1 - eLife 2017;6:e25366 DO - 10.7554/eLife.25366 UR - https://doi.org/10.7554/eLife.25366 AB - Faithfull genome partitioning during cell division relies on the Spindle Assembly Checkpoint (SAC), a conserved signaling pathway that delays anaphase onset until all chromosomes are attached to spindle microtubules. Mps1 kinase is an upstream SAC regulator that promotes the assembly of an anaphase inhibitor through a sequential multi-target phosphorylation cascade. Thus, the SAC is highly responsive to Mps1, whose activity peaks in early mitosis as a result of its T-loop autophosphorylation. However, the mechanism controlling Mps1 inactivation once kinetochores attach to microtubules and the SAC is satisfied remains unknown. Here we show in vitro and in Drosophila that Protein Phosphatase 1 (PP1) inactivates Mps1 by dephosphorylating its T-loop. PP1-mediated dephosphorylation of Mps1 occurs at kinetochores and in the cytosol, and inactivation of both pools of Mps1 during metaphase is essential to ensure prompt and efficient SAC silencing. Overall, our findings uncover a mechanism of SAC inactivation required for timely mitotic exit. KW - PP1 KW - Mps1 KW - kinetochore KW - cytosol KW - spindle assembly checkpoint KW - cell cycle JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -