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The Role of Chaperone-Mediated Autophagy in Cell Cycle Control and Its Implications in Cancer

The cell cycle involves a network of proteins that modulate the sequence and timing of proliferation events. Unregulated proliferation is the most fundamental hallmark of cancer; thus, changes in cell cycle control are at the heart of malignant transformation processes. Several cellular processes ca...

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Autores principales: Andrade-Tomaz, Marina, de Souza, Izadora, Ribeiro Reily Rocha, Clarissa, Rodrigues Gomes, Luciana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565978/
https://www.ncbi.nlm.nih.gov/pubmed/32971884
http://dx.doi.org/10.3390/cells9092140
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author Andrade-Tomaz, Marina
de Souza, Izadora
Ribeiro Reily Rocha, Clarissa
Rodrigues Gomes, Luciana
author_facet Andrade-Tomaz, Marina
de Souza, Izadora
Ribeiro Reily Rocha, Clarissa
Rodrigues Gomes, Luciana
author_sort Andrade-Tomaz, Marina
collection PubMed
description The cell cycle involves a network of proteins that modulate the sequence and timing of proliferation events. Unregulated proliferation is the most fundamental hallmark of cancer; thus, changes in cell cycle control are at the heart of malignant transformation processes. Several cellular processes can interfere with the cell cycle, including autophagy, the catabolic pathway involved in degradation of intracellular constituents in lysosomes. According to the mechanism used to deliver cargo to the lysosome, autophagy can be classified as macroautophagy (MA), microautophagy (MI), or chaperone-mediated autophagy (CMA). Distinct from other autophagy types, CMA substrates are selectively recognized by a cytosolic chaperone, one-by-one, and then addressed for degradation in lysosomes. The function of MA in cell cycle control, and its influence in cancer progression, are already well-established. However, regulation of the cell cycle by CMA, in the context of tumorigenesis, has not been fully addressed. This review aims to present and debate the molecular mechanisms by which CMA can interfere in the cell cycle, in the context of cancer. Thus, cell cycle modulators, such as MYC, hypoxia-inducible factor-1 subunit alpha (HIF-1α), and checkpoint kinase 1 (CHK1), regulated by CMA activity will be discussed. Finally, the review will focus on how CMA dysfunction may impact the cell cycle, and as consequence promote tumorigenesis.
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spelling pubmed-75659782020-10-26 The Role of Chaperone-Mediated Autophagy in Cell Cycle Control and Its Implications in Cancer Andrade-Tomaz, Marina de Souza, Izadora Ribeiro Reily Rocha, Clarissa Rodrigues Gomes, Luciana Cells Review The cell cycle involves a network of proteins that modulate the sequence and timing of proliferation events. Unregulated proliferation is the most fundamental hallmark of cancer; thus, changes in cell cycle control are at the heart of malignant transformation processes. Several cellular processes can interfere with the cell cycle, including autophagy, the catabolic pathway involved in degradation of intracellular constituents in lysosomes. According to the mechanism used to deliver cargo to the lysosome, autophagy can be classified as macroautophagy (MA), microautophagy (MI), or chaperone-mediated autophagy (CMA). Distinct from other autophagy types, CMA substrates are selectively recognized by a cytosolic chaperone, one-by-one, and then addressed for degradation in lysosomes. The function of MA in cell cycle control, and its influence in cancer progression, are already well-established. However, regulation of the cell cycle by CMA, in the context of tumorigenesis, has not been fully addressed. This review aims to present and debate the molecular mechanisms by which CMA can interfere in the cell cycle, in the context of cancer. Thus, cell cycle modulators, such as MYC, hypoxia-inducible factor-1 subunit alpha (HIF-1α), and checkpoint kinase 1 (CHK1), regulated by CMA activity will be discussed. Finally, the review will focus on how CMA dysfunction may impact the cell cycle, and as consequence promote tumorigenesis. MDPI 2020-09-22 /pmc/articles/PMC7565978/ /pubmed/32971884 http://dx.doi.org/10.3390/cells9092140 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Andrade-Tomaz, Marina
de Souza, Izadora
Ribeiro Reily Rocha, Clarissa
Rodrigues Gomes, Luciana
The Role of Chaperone-Mediated Autophagy in Cell Cycle Control and Its Implications in Cancer
title The Role of Chaperone-Mediated Autophagy in Cell Cycle Control and Its Implications in Cancer
title_full The Role of Chaperone-Mediated Autophagy in Cell Cycle Control and Its Implications in Cancer
title_fullStr The Role of Chaperone-Mediated Autophagy in Cell Cycle Control and Its Implications in Cancer
title_full_unstemmed The Role of Chaperone-Mediated Autophagy in Cell Cycle Control and Its Implications in Cancer
title_short The Role of Chaperone-Mediated Autophagy in Cell Cycle Control and Its Implications in Cancer
title_sort role of chaperone-mediated autophagy in cell cycle control and its implications in cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565978/
https://www.ncbi.nlm.nih.gov/pubmed/32971884
http://dx.doi.org/10.3390/cells9092140
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