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Protein phosphatase 1 is essential for Greatwall inactivation at mitotic exit
Author(s) -
Heim Andreas,
Konietzny Anja,
Mayer Thomas U
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201540876
Subject(s) - mitosis , microbiology and biotechnology , mitotic exit , chemistry , phosphatase , biology , biochemistry , cell division , cell , phosphorylation , spindle apparatus
Entry into mitosis is mediated by the phosphorylation of key cell cycle regulators by cyclin‐dependent kinase 1 (Cdk1). In Xenopus embryos, the M‐phase‐promoting activity of Cdk1 is antagonized by protein phosphatase PP 2A‐B55. Hence, to ensure robust cell cycle transitions, Cdk1 and PP 2A‐B55 must be regulated so that their activities are mutually exclusive. The mechanism underlying PP 2A‐B55 inactivation at mitotic entry is well understood: Cdk1‐activated Greatwall (Gwl) kinase phosphorylates Ensa/Arpp19, thereby enabling them to bind to and inhibit PP 2A‐B55. However, the re‐activation of PP 2A‐B55 during mitotic exit, which is essential for cell cycle progression, is less well understood. Here, we identify protein phosphatase PP 1 as an essential component of the PP 2A‐B55 re‐activation pathway in Xenopus embryo extracts. PP 1 initiates the re‐activation of PP 2A‐B55 by dephosphorylating Gwl. We provide evidence that PP 1 targets the auto‐phosphorylation site of Gwl, resulting in efficient Gwl inactivation. This step is necessary to facilitate subsequent complete dephosphorylation of Gwl by PP 2A‐B55. Thus, by identifying PP 1 as the phosphatase initiating Gwl inactivation, our study provides the molecular explanation for how Cdk1 inactivation is coupled to PP 2A‐B55 re‐activation at mitotic exit.