Details

Autor(en) / Beteiligte

• Heim, Andreas
• Konietzny, Anja
• Mayer, Thomas U

Titel

Protein phosphatase 1 is essential for Greatwall inactivation at mitotic exit

Ist Teil von

• EMBO reports, 2015-11, Vol.16 (11), p.1501-1510

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2015

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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 PP2A‐B55. Hence, to ensure robust cell cycle transitions, Cdk1 and PP2A‐B55 must be regulated so that their activities are mutually exclusive. The mechanism underlying PP2A‐B55 inactivation at mitotic entry is well understood: Cdk1‐activated Greatwall (Gwl) kinase phosphorylates Ensa/Arpp19, thereby enabling them to bind to and inhibit PP2A‐B55. However, the re‐activation of PP2A‐B55 during mitotic exit, which is essential for cell cycle progression, is less well understood. Here, we identify protein phosphatase PP1 as an essential component of the PP2A‐B55 re‐activation pathway in Xenopus embryo extracts. PP1 initiates the re‐activation of PP2A‐B55 by dephosphorylating Gwl. We provide evidence that PP1 targets the auto‐phosphorylation site of Gwl, resulting in efficient Gwl inactivation. This step is necessary to facilitate subsequent complete dephosphorylation of Gwl by PP2A‐B55. Thus, by identifying PP1 as the phosphatase initiating Gwl inactivation, our study provides the molecular explanation for how Cdk1 inactivation is coupled to PP2A‐B55 re‐activation at mitotic exit. Synopsis At mitotic exit, Gwl kinase is inactivated to allow the reactivation of the Cdk1‐antagonizing phosphatase PP2A‐B55. We show that phosphatase PP1 initiates Gwl inactivation by targeting its auto‐phosphorylation site. Inactivation of Gwl kinase at mitotic exit requires protein phosphatase 1 (PP1). PP1 targets the auto‐phosphorylation site of Gwl. PP1 initiates Gwl inactivation, resulting in re‐activation of PP2A‐B55. At mitotic exit, Gwl kinase is inactivated to allow the reactivation of the Cdk1‐antagonizing phosphatase PP2A‐B55. This study shows that phosphatase PP1 initiates Gwl inactivation by targeting its auto‐phosphorylation site.