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Role of the Holoenzyme PP1-SPN in the Dephosphorylation of the RB Family of Tumor Suppressors During Cell Cycle

SIMPLE SUMMARY: Cell cycle progression is highly regulated by modulating the phosphorylation status of retinoblastoma (RB) family proteins. This process is controlled by a balance in the action of kinases, such as the complexes formed by cyclin-dependent kinases (CDKs) and cyclins, and phosphatases,...

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Autores principales: Verdugo-Sivianes, Eva M., Carnero, Amancio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124259/
https://www.ncbi.nlm.nih.gov/pubmed/34066428
http://dx.doi.org/10.3390/cancers13092226
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author Verdugo-Sivianes, Eva M.
Carnero, Amancio
author_facet Verdugo-Sivianes, Eva M.
Carnero, Amancio
author_sort Verdugo-Sivianes, Eva M.
collection PubMed
description SIMPLE SUMMARY: Cell cycle progression is highly regulated by modulating the phosphorylation status of retinoblastoma (RB) family proteins. This process is controlled by a balance in the action of kinases, such as the complexes formed by cyclin-dependent kinases (CDKs) and cyclins, and phosphatases, mainly the protein phosphatase 1 (PP1). However, while the phosphorylation of the RB family has been largely studied, its dephosphorylation is less known. Recently, the PP1-Spinophilin (SPN) holoenzyme has been described as the main phosphatase responsible for the dephosphorylation of RB proteins during the G0/G1 transition and at the end of G1. Here, we describe the regulation of the phosphorylation status of RB family proteins, giving importance not only to their inactivation by phosphorylation but also to their dephosphorylation to restore the cell cycle. ABSTRACT: Cell cycle progression is highly regulated by modulating the phosphorylation status of the retinoblastoma protein (pRB) and the other two members of the RB family, p107 and p130. This process is controlled by a balance in the action of kinases, such as the complexes formed by cyclin-dependent kinases (CDKs) and cyclins, and phosphatases, mainly the protein phosphatase 1 (PP1). However, while the phosphorylation of the RB family has been largely studied, its dephosphorylation is less known. Phosphatases are holoenzymes formed by a catalytic subunit and a regulatory protein with substrate specificity. Recently, the PP1-Spinophilin (SPN) holoenzyme has been described as the main phosphatase responsible for the dephosphorylation of RB proteins during the G0/G1 transition and at the end of G1. Moreover, SPN has been described as a tumor suppressor dependent on PP1 in lung and breast tumors, where it promotes tumorigenesis by increasing the cancer stem cell pool. Therefore, a connection between the cell cycle and stem cell biology has also been proposed via SPN/PP1/RB proteins.
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spelling pubmed-81242592021-05-17 Role of the Holoenzyme PP1-SPN in the Dephosphorylation of the RB Family of Tumor Suppressors During Cell Cycle Verdugo-Sivianes, Eva M. Carnero, Amancio Cancers (Basel) Review SIMPLE SUMMARY: Cell cycle progression is highly regulated by modulating the phosphorylation status of retinoblastoma (RB) family proteins. This process is controlled by a balance in the action of kinases, such as the complexes formed by cyclin-dependent kinases (CDKs) and cyclins, and phosphatases, mainly the protein phosphatase 1 (PP1). However, while the phosphorylation of the RB family has been largely studied, its dephosphorylation is less known. Recently, the PP1-Spinophilin (SPN) holoenzyme has been described as the main phosphatase responsible for the dephosphorylation of RB proteins during the G0/G1 transition and at the end of G1. Here, we describe the regulation of the phosphorylation status of RB family proteins, giving importance not only to their inactivation by phosphorylation but also to their dephosphorylation to restore the cell cycle. ABSTRACT: Cell cycle progression is highly regulated by modulating the phosphorylation status of the retinoblastoma protein (pRB) and the other two members of the RB family, p107 and p130. This process is controlled by a balance in the action of kinases, such as the complexes formed by cyclin-dependent kinases (CDKs) and cyclins, and phosphatases, mainly the protein phosphatase 1 (PP1). However, while the phosphorylation of the RB family has been largely studied, its dephosphorylation is less known. Phosphatases are holoenzymes formed by a catalytic subunit and a regulatory protein with substrate specificity. Recently, the PP1-Spinophilin (SPN) holoenzyme has been described as the main phosphatase responsible for the dephosphorylation of RB proteins during the G0/G1 transition and at the end of G1. Moreover, SPN has been described as a tumor suppressor dependent on PP1 in lung and breast tumors, where it promotes tumorigenesis by increasing the cancer stem cell pool. Therefore, a connection between the cell cycle and stem cell biology has also been proposed via SPN/PP1/RB proteins. MDPI 2021-05-06 /pmc/articles/PMC8124259/ /pubmed/34066428 http://dx.doi.org/10.3390/cancers13092226 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Verdugo-Sivianes, Eva M.
Carnero, Amancio
Role of the Holoenzyme PP1-SPN in the Dephosphorylation of the RB Family of Tumor Suppressors During Cell Cycle
title Role of the Holoenzyme PP1-SPN in the Dephosphorylation of the RB Family of Tumor Suppressors During Cell Cycle
title_full Role of the Holoenzyme PP1-SPN in the Dephosphorylation of the RB Family of Tumor Suppressors During Cell Cycle
title_fullStr Role of the Holoenzyme PP1-SPN in the Dephosphorylation of the RB Family of Tumor Suppressors During Cell Cycle
title_full_unstemmed Role of the Holoenzyme PP1-SPN in the Dephosphorylation of the RB Family of Tumor Suppressors During Cell Cycle
title_short Role of the Holoenzyme PP1-SPN in the Dephosphorylation of the RB Family of Tumor Suppressors During Cell Cycle
title_sort role of the holoenzyme pp1-spn in the dephosphorylation of the rb family of tumor suppressors during cell cycle
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124259/
https://www.ncbi.nlm.nih.gov/pubmed/34066428
http://dx.doi.org/10.3390/cancers13092226
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