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Regulation of Protein Degradation by Proteasomes in Cancer
Imbalance of protein homeostasis (proteostasis) is known to cause cellular malfunction, cell death, and diseases. Elaborate regulation of protein synthesis and degradation is one of the important processes in maintaining normal cellular functions. Protein degradation pathways in eukaryotes are large...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Korean Society of Cancer Prevention
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330989/ https://www.ncbi.nlm.nih.gov/pubmed/30671397 http://dx.doi.org/10.15430/JCP.2018.23.4.153 |
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author | Jang, Ho Hee |
author_facet | Jang, Ho Hee |
author_sort | Jang, Ho Hee |
collection | PubMed |
description | Imbalance of protein homeostasis (proteostasis) is known to cause cellular malfunction, cell death, and diseases. Elaborate regulation of protein synthesis and degradation is one of the important processes in maintaining normal cellular functions. Protein degradation pathways in eukaryotes are largely divided into proteasome-mediated degradation and lysosome-mediated degradation. Proteasome is a multisubunit complex that selectively degrades 80% to 90% of cellular proteins. Proteasome-mediated degradation can be divided into 26S proteasome (20S proteasome + 19S regulatory particle) and free 20S proteasome degradation. In 1980, it was discovered that during ubiquitination process, wherein ubiquitin binds to a substrate protein in an ATP-dependent manner, ubiquitin acts as a degrading signal to degrade the substrate protein via proteasome. Conversely, 20S proteasome degrades the substrate protein without using ATP or ubiquitin because it recognizes the oxidized and structurally modified hydrophobic patch of the substrate protein. To date, most studies have focused on protein degradation via 26S proteasome. This review describes the 26S/20S proteasomal pathway of protein degradation and discusses the potential of proteasome as therapeutic targets for cancer treatment as well as against diseases caused by abnormalities in the proteolytic system. |
format | Online Article Text |
id | pubmed-6330989 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Korean Society of Cancer Prevention |
record_format | MEDLINE/PubMed |
spelling | pubmed-63309892019-01-22 Regulation of Protein Degradation by Proteasomes in Cancer Jang, Ho Hee J Cancer Prev Review Imbalance of protein homeostasis (proteostasis) is known to cause cellular malfunction, cell death, and diseases. Elaborate regulation of protein synthesis and degradation is one of the important processes in maintaining normal cellular functions. Protein degradation pathways in eukaryotes are largely divided into proteasome-mediated degradation and lysosome-mediated degradation. Proteasome is a multisubunit complex that selectively degrades 80% to 90% of cellular proteins. Proteasome-mediated degradation can be divided into 26S proteasome (20S proteasome + 19S regulatory particle) and free 20S proteasome degradation. In 1980, it was discovered that during ubiquitination process, wherein ubiquitin binds to a substrate protein in an ATP-dependent manner, ubiquitin acts as a degrading signal to degrade the substrate protein via proteasome. Conversely, 20S proteasome degrades the substrate protein without using ATP or ubiquitin because it recognizes the oxidized and structurally modified hydrophobic patch of the substrate protein. To date, most studies have focused on protein degradation via 26S proteasome. This review describes the 26S/20S proteasomal pathway of protein degradation and discusses the potential of proteasome as therapeutic targets for cancer treatment as well as against diseases caused by abnormalities in the proteolytic system. Korean Society of Cancer Prevention 2018-12 2018-12-30 /pmc/articles/PMC6330989/ /pubmed/30671397 http://dx.doi.org/10.15430/JCP.2018.23.4.153 Text en Copyright © 2018 Korean Society of Cancer Prevention This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Jang, Ho Hee Regulation of Protein Degradation by Proteasomes in Cancer |
title | Regulation of Protein Degradation by Proteasomes in Cancer |
title_full | Regulation of Protein Degradation by Proteasomes in Cancer |
title_fullStr | Regulation of Protein Degradation by Proteasomes in Cancer |
title_full_unstemmed | Regulation of Protein Degradation by Proteasomes in Cancer |
title_short | Regulation of Protein Degradation by Proteasomes in Cancer |
title_sort | regulation of protein degradation by proteasomes in cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330989/ https://www.ncbi.nlm.nih.gov/pubmed/30671397 http://dx.doi.org/10.15430/JCP.2018.23.4.153 |
work_keys_str_mv | AT janghohee regulationofproteindegradationbyproteasomesincancer |