Inhibitor-2 (I2) ranks amongst the most ancient regulators of protein phosphatase-1 (PP1). It is a small, intrinsically disordered protein that was originally discovered as a potent inhibitor of PP1. However, later investigations also characterized I2 as an activator of PP1 as well as a chaperone for PP1 folding. Numerous studies disclosed the importance of I2 for diverse cellular processes but did not describe a unifying molecular principle of PP1 regulation. We have re-analyzed the literature on I2 in the light of current insights of PP1 structure and regulation. Extensive biochemical data, largely ignored in the recent I2 literature, provide substantial indirect evidence for a role of I2 as a loader of active-site metals. In addition, I2 appears to function as a competitive inhibitor of PP1 in higher eukaryotes. The published data also demonstrate that several segments of I2 that remain unstructured in the PP1 : I2 complex are in fact essential for PP1 regulation. Together, the available data identify I2 as a dynamic activity-modulator of PP1.
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October 2020
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Cover Image
Centrosomes are microtubule-organizing centres required for the asymmetric division of neural stem cells, which support neurodevelopment, as discussed in a mini-review by Robinson and colleagues (pages 2101–2115) In the cover image, microtubules are shown in yellow and neural stem cells (aPKC) are magenta. Image provided by Dorothy Lerit.
Review Article|
October 14 2020
Protein phosphatase-1: dual activity regulation by Inhibitor-2
Sarah Lemaire
;
Sarah Lemaire
Laboratory of Biosignaling and Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, B-3000 Leuven, Belgium
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Mathieu Bollen
Laboratory of Biosignaling and Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, B-3000 Leuven, Belgium
Correspondence: Mathieu Bollen (Mathieu.Bollen@kuleuven.be)
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Publisher: Portland Press Ltd
Received:
August 04 2020
Revision Received:
September 15 2020
Accepted:
September 16 2020
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem Soc Trans (2020) 48 (5): 2229–2240.
Article history
Received:
August 04 2020
Revision Received:
September 15 2020
Accepted:
September 16 2020
Citation
Sarah Lemaire, Mathieu Bollen; Protein phosphatase-1: dual activity regulation by Inhibitor-2. Biochem Soc Trans 30 October 2020; 48 (5): 2229–2240. doi: https://doi.org/10.1042/BST20200503
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