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Author(s): Moura, M
Osswald, M
Leça, N
Barbosa, J
Pereira, AJ
Maiato, H
Sunkel, CE
Conde, C
Title: Protein Phosphatase 1 inactivates Mps1 to ensure efficient Spindle Assembly Checkpoint silencing
Publisher: eLife Sciences Publications
Issue Date: 2017
Abstract: 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.
Subject: Animals
Cell Cycle Proteins/metabolism
Cell Division
Chromosome Segregation
Drosophila Proteins/metabolism
M Phase Cell Cycle Checkpoints
Protein Phosphatase 1/metabolism
Protein-Serine-Threonine Kinases/metabolism
Source: Elife, 2, vol. 6. pii: e25366
Related Information: info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F87871%2F2012/PT
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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