Protein Phosphatase 1 inactivates Mps1 to ensure efficient Spindle Assembly Checkpoint silencing

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Moura, M (Author) Other; Osswald, M (Author) Other; Leca, N (Author) Other; Barbosa, J (Author) Other; Pereira, AJ (Author) Other; Helder Maiato (Author) FMUP; Sunkel, CE (Author) ICBAS; Conde, C (Author) Other

Journal

Title: eLife

Vol. 6

ISSN: 2050-084X

Publisher: eLife Sciences Publications

Indexing

ISI Web of Knowledge - 35 Citations

Scopus - 34 Citations

Other information

Authenticus ID: P-00M-VYX

DOI: 10.7554/elife.25366

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 29