Protein phosphatases and the regulation of mitosis

Francis A Barr,Paul R Elliott,Ulrike Gruneberg

doi:10.1242/jcs.087106

Francis A Barr, Paul R Elliott + Show 1 more

Open Access

https://doi.org/10.1242/jcs.087106

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Abstract

Dynamic control of protein phosphorylation is necessary for the regulation of many cellular processes, including mitosis and cytokinesis. Indeed, although the central role of protein kinases is widely appreciated and intensely studied, the importance of protein phosphatases is often overlooked. Recent studies, however, have highlighted the considerable role of protein phosphatases in both the spatial and temporal control of protein kinase activity, and the modulation of substrate phosphorylation. Here, we will focus on recent advances in our understanding of phosphatase structure, and the importance of phosphatase function in the control of mitotic spindle formation, chromosome architecture and cohesion, and cell division.

Highlights

Post-translational modifications are crucial for the control of the remarkable changes in cellular architecture that are observed as cells enter and exit mitosis
Protein phosphorylation is typically a short-lived highly dynamic modification and, in recent years, important roles in mitosis have begun to emerge for specific protein phosphatases (Chen et al, 2007; Gharbi-Ayachi et al, 2010; Kitajima et al, 2006; Mochida et al, 2009; Mochida et al, 2010; Riedel et al, 2006; Zeng et al, 2010)
PP6 has a similar architecture to PP2A, with an ankyrin repeat domain subunit and a SIT4 phosphatase-associated protein (SAPS) domain scaffolding subunit (Stefansson and Brautigan, 2006; Stefansson et al, 2008), whereas PP4 is thought to possess a single regulatory subunit (Chen et al, 2008)

Summary

Introduction

Post-translational modifications are crucial for the control of the remarkable changes in cellular architecture that are observed as cells enter and exit mitosis. PP6 has a similar architecture to PP2A, with an ankyrin repeat domain subunit and a SIT4 phosphatase-associated protein (SAPS) domain scaffolding subunit (Stefansson and Brautigan, 2006; Stefansson et al, 2008), whereas PP4 is thought to possess a single regulatory subunit (Chen et al, 2008) This makes it possible for a relatively small number of catalytic subunits to form a multitude of functionally distinct holoenzymes with unique substrate specificity, regulatory properties and localization within the cell. Binding of these regulatory subunits has the dual role of directing phosphatase activity towards a specific substrate, and reducing its activity towards other phosphorylated proteins (Agostinis et al, 1992; Imaoka et al, 1983; Mumby et al, 1987). The best examples in the context of mitosis are the PP1 –Repo-man

E PP2A–substrate recognition BЈγ-subunit Substrate binding

D Organelle reassembly