Chk1 modulates the interaction between myosin phosphatase targeting protein 1 (MYPT1) and protein phosphatase 1c? (PP1c?).
Polo-like kinase 1 (Plk1) is an instrumental kinase that modulates many aspects of the cell cycle. Previous investigations have indicated that Plk1 is a target of the DNA damage response, and Plk1 inhibition is dependent on ATM/ATR and Chk1. But the exact mechanism remains elusive. In a proteomic screen to ... identify Chk1-interacting proteins, we found that myosin phosphatase targeting protein 1 (MYPT1) was present in the immunocomplex. MYPT1 is phosphorylated by CDK1, thus recruiting protein phosphatase 1? (PP1c?) to dephosphorylate and inactivate Plk1. Here we identified that Chk1 directly interacts with MYPT1 and preferentially phosphorylates MYPT1 at Ser20, which is essential for MYPT1-PP1c? interaction and subsequent Plk1 dephosphorylation. Phosphorylation of Ser20 is abolished during mitotic damage when Chk1 is inhibited. The degradation of MYPT1 is also regulated by Chk1 phosphorylation. Our results thus unveil the underlying machinery that attenuates Plk1 activity during mitotic damage through Chk1-induced phosphorylation of MYPT1.
Mesh Terms:
Amino Acid Sequence, Animals, Ataxia Telangiectasia Mutated Proteins, CDC2 Protein Kinase, Cell Cycle Proteins, HEK293 Cells, HeLa Cells, Humans, Mitosis, Myosin-Light-Chain Phosphatase, Phosphopeptides, Phosphorylation, Protein Binding, Protein Phosphatase 1, Protein Serine-Threonine Kinases, Proteomics, Proto-Oncogene Proteins, Serine
Amino Acid Sequence, Animals, Ataxia Telangiectasia Mutated Proteins, CDC2 Protein Kinase, Cell Cycle Proteins, HEK293 Cells, HeLa Cells, Humans, Mitosis, Myosin-Light-Chain Phosphatase, Phosphopeptides, Phosphorylation, Protein Binding, Protein Phosphatase 1, Protein Serine-Threonine Kinases, Proteomics, Proto-Oncogene Proteins, Serine
Cell Cycle
Date: Dec. 22, 2017
PubMed ID: 29262732
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