Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression

Cellular processes are dictated by the active signaling of proteins relaying messages to regulate cell proliferation, apoptosis, signal transduction and cell communications. An intricate web of protein kinases and phosphatases are critical to the proper transmission of signals across such cascades....

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Main Authors: Raman, D., Pervaiz, Shazib
Format: Journal Article
Published: Elsevier BV 2019
Online Access:http://hdl.handle.net/20.500.11937/74776
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author Raman, D.
Pervaiz, Shazib
author_facet Raman, D.
Pervaiz, Shazib
author_sort Raman, D.
building Curtin Institutional Repository
collection Online Access
description Cellular processes are dictated by the active signaling of proteins relaying messages to regulate cell proliferation, apoptosis, signal transduction and cell communications. An intricate web of protein kinases and phosphatases are critical to the proper transmission of signals across such cascades. By governing 30–50% of all protein dephosphorylation in the cell, with prominent substrate proteins being key regulators of signaling cascades, the phosphatase PP2A has emerged as a celebrated player in various developmental and tumorigenic pathways, thereby posing as an attractive target for therapeutic intervention in various pathologies wherein its activity is deregulated. This review is mainly focused on refreshing our understanding of the structural and functional complexity that cocoons the PP2A phosphatase, and its expression in cancers. Additionally, we focus on its physiological regulation as well as into recent advents and strategies that have shown promise in countering the deregulation of the phosphatase through its targeted reactivation. Finally, we dwell upon one of the key regulators of PP2A in cancer cells-cellular redox status-its multifarious nature, and its integration into the reactome of PP2A, highlighting some of the significant impacts that ROS can inflict on the structural modifications and functional aspect of PP2A.
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spelling curtin-20.500.11937-747762019-05-10T02:32:51Z Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression Raman, D. Pervaiz, Shazib Cellular processes are dictated by the active signaling of proteins relaying messages to regulate cell proliferation, apoptosis, signal transduction and cell communications. An intricate web of protein kinases and phosphatases are critical to the proper transmission of signals across such cascades. By governing 30–50% of all protein dephosphorylation in the cell, with prominent substrate proteins being key regulators of signaling cascades, the phosphatase PP2A has emerged as a celebrated player in various developmental and tumorigenic pathways, thereby posing as an attractive target for therapeutic intervention in various pathologies wherein its activity is deregulated. This review is mainly focused on refreshing our understanding of the structural and functional complexity that cocoons the PP2A phosphatase, and its expression in cancers. Additionally, we focus on its physiological regulation as well as into recent advents and strategies that have shown promise in countering the deregulation of the phosphatase through its targeted reactivation. Finally, we dwell upon one of the key regulators of PP2A in cancer cells-cellular redox status-its multifarious nature, and its integration into the reactome of PP2A, highlighting some of the significant impacts that ROS can inflict on the structural modifications and functional aspect of PP2A. 2019 Journal Article http://hdl.handle.net/20.500.11937/74776 10.1016/j.redox.2019.101105 http://creativecommons.org/licenses/by-nc-nd/4.0/ Elsevier BV fulltext
spellingShingle Raman, D.
Pervaiz, Shazib
Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression
title Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression
title_full Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression
title_fullStr Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression
title_full_unstemmed Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression
title_short Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression
title_sort redox inhibition of protein phosphatase pp2a: potential implications in oncogenesis and its progression
url http://hdl.handle.net/20.500.11937/74776