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TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14

The proteasome is a complex protease critical for protein quality control and cell regulation, and its dysfunction is associated with cancer and other diseases. However, the mechanisms that control proteasome activity  in normal and malignant cells remain unclear. Here we report that TRIM11 enhances...

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Autores principales: Chen, Liang, Zhu, Guixin, Johns, Eleanor M., Yang, Xiaolu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964324/
https://www.ncbi.nlm.nih.gov/pubmed/29581427
http://dx.doi.org/10.1038/s41467-018-03499-z
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author Chen, Liang
Zhu, Guixin
Johns, Eleanor M.
Yang, Xiaolu
author_facet Chen, Liang
Zhu, Guixin
Johns, Eleanor M.
Yang, Xiaolu
author_sort Chen, Liang
collection PubMed
description The proteasome is a complex protease critical for protein quality control and cell regulation, and its dysfunction is associated with cancer and other diseases. However, the mechanisms that control proteasome activity  in normal and malignant cells remain unclear. Here we report that TRIM11 enhances degradation of aberrant and normal regulatory proteins, and augments overall rate of proteolysis. Mechanistically, TRIM11 binds to both the proteasome and USP14, a deubiquitinase that prematurely removes ubiquitins from proteasome-bound substrates and also noncatalytically inhibits the proteasome, and precludes their association, thereby increasing proteasome activity. TRIM11 promotes cell survival and is upregulated upon heat shock. Moreover, TRIM11 is required for tumor growth, and increased expression of TRIM11 correlates with poor clinical survival. These findings identify TRIM11 as an important activator of the proteasome, define a pathway that adjusts proteasome activity, and reveal a mechanism by which tumor cells acquire higher degradative power to support oncogenic growth.
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spelling pubmed-59643242018-05-24 TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14 Chen, Liang Zhu, Guixin Johns, Eleanor M. Yang, Xiaolu Nat Commun Article The proteasome is a complex protease critical for protein quality control and cell regulation, and its dysfunction is associated with cancer and other diseases. However, the mechanisms that control proteasome activity  in normal and malignant cells remain unclear. Here we report that TRIM11 enhances degradation of aberrant and normal regulatory proteins, and augments overall rate of proteolysis. Mechanistically, TRIM11 binds to both the proteasome and USP14, a deubiquitinase that prematurely removes ubiquitins from proteasome-bound substrates and also noncatalytically inhibits the proteasome, and precludes their association, thereby increasing proteasome activity. TRIM11 promotes cell survival and is upregulated upon heat shock. Moreover, TRIM11 is required for tumor growth, and increased expression of TRIM11 correlates with poor clinical survival. These findings identify TRIM11 as an important activator of the proteasome, define a pathway that adjusts proteasome activity, and reveal a mechanism by which tumor cells acquire higher degradative power to support oncogenic growth. Nature Publishing Group UK 2018-03-26 /pmc/articles/PMC5964324/ /pubmed/29581427 http://dx.doi.org/10.1038/s41467-018-03499-z Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chen, Liang
Zhu, Guixin
Johns, Eleanor M.
Yang, Xiaolu
TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14
title TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14
title_full TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14
title_fullStr TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14
title_full_unstemmed TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14
title_short TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14
title_sort trim11 activates the proteasome and promotes overall protein degradation by regulating usp14
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964324/
https://www.ncbi.nlm.nih.gov/pubmed/29581427
http://dx.doi.org/10.1038/s41467-018-03499-z
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