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14-3-3 Proteins are Regulators of Autophagy
14-3-3 proteins are implicated in the regulation of proteins involved in a variety of signaling pathways. 14-3-3-dependent protein regulation occurs through phosphorylation-dependent binding that results, in many cases, in the release of survival signals in cells. Autophagy is a cell digestion proce...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901138/ https://www.ncbi.nlm.nih.gov/pubmed/24710529 http://dx.doi.org/10.3390/cells1040754 |
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author | Pozuelo-Rubio, Mercedes |
author_facet | Pozuelo-Rubio, Mercedes |
author_sort | Pozuelo-Rubio, Mercedes |
collection | PubMed |
description | 14-3-3 proteins are implicated in the regulation of proteins involved in a variety of signaling pathways. 14-3-3-dependent protein regulation occurs through phosphorylation-dependent binding that results, in many cases, in the release of survival signals in cells. Autophagy is a cell digestion process that contributes to overcoming nutrient deprivation and is initiated under stress conditions. However, whether autophagy is a cell survival or cell death mechanism remains under discussion and may depend on context. Nevertheless, autophagy is a cellular process that determines cell fate and is tightly regulated by different signaling pathways, some of which, for example MAPK, PI3K and mTOR, are tightly regulated by 14-3-3 proteins. It is therefore important to understand the role of 14-3-3 protein in modulating the autophagic process. Within this context, direct binding of 14-3-3 to mTOR regulatory proteins, such as TSC2 and PRAS40, connects 14-3-3 with autophagy regulatory processes. In addition, 14-3-3 binding to human vacuolar protein sorting 34 (hVps34), a class III phosphatidylinositol-3-kinase (PI3KC3), indicates the involvement of 14-3-3 proteins in regulating autophagosome formation. hVps34 is involved in vesicle trafficking processes such as autophagy, and its activation is needed for initiation of autophagy. Chromatography and overlay techniques suggest that hVps34 directly interacts with 14-3-3 proteins under physiological conditions, thereby maintaining hVps34 in an inactive state. In contrast, nutrient starvation promotes dissociation of the 14-3-3–hVps34 complex, thereby enhancing hVps34 lipid kinase activity. Thus, 14-3-3 proteins are regulators of autophagy through regulating key components of the autophagic machinery. This review summarizes the role of 14-3-3 protein in the control of target proteins involved in regulating the master switches of autophagy. |
format | Online Article Text |
id | pubmed-3901138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-39011382014-04-07 14-3-3 Proteins are Regulators of Autophagy Pozuelo-Rubio, Mercedes Cells Review 14-3-3 proteins are implicated in the regulation of proteins involved in a variety of signaling pathways. 14-3-3-dependent protein regulation occurs through phosphorylation-dependent binding that results, in many cases, in the release of survival signals in cells. Autophagy is a cell digestion process that contributes to overcoming nutrient deprivation and is initiated under stress conditions. However, whether autophagy is a cell survival or cell death mechanism remains under discussion and may depend on context. Nevertheless, autophagy is a cellular process that determines cell fate and is tightly regulated by different signaling pathways, some of which, for example MAPK, PI3K and mTOR, are tightly regulated by 14-3-3 proteins. It is therefore important to understand the role of 14-3-3 protein in modulating the autophagic process. Within this context, direct binding of 14-3-3 to mTOR regulatory proteins, such as TSC2 and PRAS40, connects 14-3-3 with autophagy regulatory processes. In addition, 14-3-3 binding to human vacuolar protein sorting 34 (hVps34), a class III phosphatidylinositol-3-kinase (PI3KC3), indicates the involvement of 14-3-3 proteins in regulating autophagosome formation. hVps34 is involved in vesicle trafficking processes such as autophagy, and its activation is needed for initiation of autophagy. Chromatography and overlay techniques suggest that hVps34 directly interacts with 14-3-3 proteins under physiological conditions, thereby maintaining hVps34 in an inactive state. In contrast, nutrient starvation promotes dissociation of the 14-3-3–hVps34 complex, thereby enhancing hVps34 lipid kinase activity. Thus, 14-3-3 proteins are regulators of autophagy through regulating key components of the autophagic machinery. This review summarizes the role of 14-3-3 protein in the control of target proteins involved in regulating the master switches of autophagy. MDPI 2012-10-15 /pmc/articles/PMC3901138/ /pubmed/24710529 http://dx.doi.org/10.3390/cells1040754 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Review Pozuelo-Rubio, Mercedes 14-3-3 Proteins are Regulators of Autophagy |
title | 14-3-3 Proteins are Regulators of Autophagy |
title_full | 14-3-3 Proteins are Regulators of Autophagy |
title_fullStr | 14-3-3 Proteins are Regulators of Autophagy |
title_full_unstemmed | 14-3-3 Proteins are Regulators of Autophagy |
title_short | 14-3-3 Proteins are Regulators of Autophagy |
title_sort | 14-3-3 proteins are regulators of autophagy |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901138/ https://www.ncbi.nlm.nih.gov/pubmed/24710529 http://dx.doi.org/10.3390/cells1040754 |
work_keys_str_mv | AT pozuelorubiomercedes 1433proteinsareregulatorsofautophagy |