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Cancers 2015, 7(2), 648-669;

PP2A: The Wolf in Sheep’s Clothing?

Department of Life Sciences, and Materials and Surface Science Institute, University of Limerick, Limerick 78666, Ireland
Stokes Institute, University of Limerick 78666, Limerick, Ireland
Author to whom correspondence should be addressed.
Academic Editor: Hiromi I. Wettersten
Received: 27 January 2015 / Revised: 16 March 2015 / Accepted: 23 March 2015 / Published: 10 April 2015
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Protein Phosphatase 2A (PP2A) is a major serine/threonine phosphatase in cells. It consists of a catalytic subunit (C), a structural subunit (A), and a regulatory/variable B-type subunit. PP2A has a critical role to play in homeostasis where its predominant function is as a phosphatase that regulates the major cell signaling pathways in cells. Changes in the assembly, activity and substrate specificity of the PP2A holoenzyme have a direct role in disease and are a major contributor to the maintenance of the transformed phenotype in cancer. We have learned a lot about how PP2A functions from specific mutations that disrupt the core assembly of PP2A and from viral proteins that target PP2A and inhibit its effect as a phosphatase. This prompted various studies revealing that restoration of PP2A activity benefits some cancer patients. However, our understanding of the mechanism of action of this is limited because of the complex nature of PP2A holoenzyme assembly and because it acts through a wide variety of signaling pathways. Information on PP2A is also conflicting as there are situations whereby inactivation of PP2A induces apoptosis in many cancer cells. In this review we discuss this relationship and we also address many of the pertinent and topical questions that relate to novel therapeutic strategies aimed at altering PP2A activity. View Full-Text
Keywords: phosphatase; PP2A; cellular signaling; tumour suppressor; cancer phosphatase; PP2A; cellular signaling; tumour suppressor; cancer

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Kiely, M.; Kiely, P.A. PP2A: The Wolf in Sheep’s Clothing? Cancers 2015, 7, 648-669.

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