Regulation of proteasome assembly and activity in health and disease

Adrien Rousseau, Anne Bertolotti (Lead / Corresponding author)

Research output: Contribution to journalReview article

21 Citations (Scopus)
156 Downloads (Pure)

Abstract

The proteasome degrades most cellular proteins in a controlled and tightly regulated manner and thereby controls many processes, including cell cycle, transcription, signalling, trafficking and protein quality control. Proteasomal degradation is vital in all cells and organisms, and dysfunction or failure of proteasomal degradation is associated with diverse human diseases, including cancer and neurodegeneration. Target selection is an important and well-established way to control protein degradation. In addition, mounting evidence indicates that cells adjust proteasome-mediated degradation to their needs by regulating proteasome abundance through the coordinated expression of proteasome subunits and assembly chaperones. Central to the regulation of proteasome assembly is TOR complex 1 (TORC1), which is the master regulator of cell growth and stress. This Review discusses how proteasome assembly and the regulation of proteasomal degradation are integrated with cellular physiology, including the interplay between the proteasome and autophagy pathways. Understanding these mechanisms has potential implications for disease therapy, as the misregulation of proteasome function contributes to human diseases such as cancer and neurodegeneration.

Original languageEnglish
Pages (from-to)697-712
Number of pages16
JournalNature Reviews Molecular Cell Biology
Volume19
Issue number11
Early online date31 Jul 2018
DOIs
Publication statusPublished - 2018

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Proteasome Endopeptidase Complex
Health
Autophagy
Protein Transport
Quality Control
Proteolysis
Neoplasms
Cell Cycle
Growth

Cite this

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title = "Regulation of proteasome assembly and activity in health and disease",
abstract = "The proteasome degrades most cellular proteins in a controlled and tightly regulated manner and thereby controls many processes, including cell cycle, transcription, signalling, trafficking and protein quality control. Proteasomal degradation is vital in all cells and organisms, and dysfunction or failure of proteasomal degradation is associated with diverse human diseases, including cancer and neurodegeneration. Target selection is an important and well-established way to control protein degradation. In addition, mounting evidence indicates that cells adjust proteasome-mediated degradation to their needs by regulating proteasome abundance through the coordinated expression of proteasome subunits and assembly chaperones. Central to the regulation of proteasome assembly is TOR complex 1 (TORC1), which is the master regulator of cell growth and stress. This Review discusses how proteasome assembly and the regulation of proteasomal degradation are integrated with cellular physiology, including the interplay between the proteasome and autophagy pathways. Understanding these mechanisms has potential implications for disease therapy, as the misregulation of proteasome function contributes to human diseases such as cancer and neurodegeneration.",
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note = "The authors’ laboratory is supported by the Medical Research Council (UK) MC_U105185860. A.B. is an honorary fellow of the University of Cambridge Clinical Neurosciences Department. A.R. was supported by a European Molecular Biology Organization (EMBO) long-term fellowship and an EMBO advanced fellowship.",
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Regulation of proteasome assembly and activity in health and disease. / Rousseau, Adrien; Bertolotti, Anne (Lead / Corresponding author).

In: Nature Reviews Molecular Cell Biology, Vol. 19, No. 11, 2018, p. 697-712.

Research output: Contribution to journalReview article

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AU - Rousseau, Adrien

AU - Bertolotti, Anne

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PY - 2018

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AB - The proteasome degrades most cellular proteins in a controlled and tightly regulated manner and thereby controls many processes, including cell cycle, transcription, signalling, trafficking and protein quality control. Proteasomal degradation is vital in all cells and organisms, and dysfunction or failure of proteasomal degradation is associated with diverse human diseases, including cancer and neurodegeneration. Target selection is an important and well-established way to control protein degradation. In addition, mounting evidence indicates that cells adjust proteasome-mediated degradation to their needs by regulating proteasome abundance through the coordinated expression of proteasome subunits and assembly chaperones. Central to the regulation of proteasome assembly is TOR complex 1 (TORC1), which is the master regulator of cell growth and stress. This Review discusses how proteasome assembly and the regulation of proteasomal degradation are integrated with cellular physiology, including the interplay between the proteasome and autophagy pathways. Understanding these mechanisms has potential implications for disease therapy, as the misregulation of proteasome function contributes to human diseases such as cancer and neurodegeneration.

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