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Peer-reviewedCC BYAutophagy

Survey of the human proteostasis network: the ubiquitin-proteasome system

  • Suzanne Elsasser1,2
  • Evan T. Powers2,3
  • Thomas Stoeger4,5,6,2
  • Xiaojing Sui5,2
  • Roy D. Kurtzbard7,5,2
  • Patricia Martínez-Botía8,2
  • Margaret A. Wangeline9,2
  • Alejandro Rodríguez Gama5,2
  • Edward L. Huttlin1
  • Lisa P. Elia10,2
  • Jeffery W. Kelly2,3
  • Jason E. Gestwicki2,11
8 more authors
  • Judith Frydman9,2
  • Steven M. Finkbeiner10,12,2,13
  • Eugenia M. Clérico5,2
  • Richard I. Morimoto5,2
  • Miguel A. Prado8,2
  • Alfred C.O. Vertegaal14
  • Kay Hofmann15
  • Daniel J. Finley1,2
15 affiliations
  1. 1Harvard Medical School
  2. 2The Proteostasis Consortium
  3. 3The Scripps Research Institute
  4. 4NSF-Simons National Institute for Theory and Mathematics in Biology (NITMB)
  5. 5Northwestern University
  6. 6Simpson Querrey Lung Institute for Translational Science, Feinberg School of Medicine, Northwestern University
  7. 7MRC Toxicology Unit, University of Cambridge
  8. 8Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)
  9. 9Stanford University
  10. 10Center for Systems and Therapeutics, The J. David Gladstone Institutes
  11. 11University of California San Francisco
  12. 12Taube/Koret Center for Neurodegenerative Disease, The J. David Gladstone Institutes
  13. 13UCSF
  14. 14Leiden University Medical Center
  15. 15University of Cologne
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Abstract

Modification by ubiquitination governs the half-lives of thousands of proteins that are fated for elimination by either the proteasome or autophagy pathways, depending on the intricate architectures of ubiquitin modification. This system mediates quality control for individual proteins, protein complexes, and organelles, as well as myriad purely regulatory functions. Here we provide a comprehensive survey of the ubiquitin-proteasome system (UPS), the scope of which is at present poorly defined. The UPS, with the inclusion of pathways involving ubiquitin-like modifiers, comprises in our estimate over 1430 distinct components in humans, a vast set of activities whose collective impact on the biology of the cell is pervasive. The UPS is an integral component of the proteostasis network (PN), the remainder of which is surveyed in the accompanying reports. With the addition of molecular chaperones, proteins from autophagy-lysosome pathway, and related activities, the PN includes in total over 3150 components by our estimates. Comprehensive and systematic definition of these pathways should facilitate a range of ongoing investigations in the areas of genomics, proteomics, biochemistry, cell biology, and disease research.Abbreviations: APC, anaphase promoting complex; CDD, Conserved Domain Database; CRL, cullin RING ligase; DSB, double-strand break; DUB, deubiquitinating enzyme; ERAD, ER-associated degradation; PN, proteostasis network; RBR, RING-between-RING; RCR, RING-Cys-Relay; SPOC, Structure Prediction and Omics-informed Classifier; UB, ubiquitin; UBL, ubiquitin-like; UBLM, ubiquitin-like modifier; UEV, ubiquitin-conjugating enzyme variant; UPS, ubiquitin-proteasome system

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Cite

BibTeXRIS
BibTeX
@article{elsasser2026survey,
  title = {{Survey of the human proteostasis network: the ubiquitin-proteasome system}},
  author = {Suzanne Elsasser and Evan T. Powers and Thomas Stoeger and Xiaojing Sui and Roy D. Kurtzbard and Patricia Martínez-Botía and Margaret A. Wangeline and Alejandro Rodríguez Gama and Edward L. Huttlin and Lisa P. Elia and Jeffery W. Kelly and Jason E. Gestwicki and Judith Frydman and Steven M. Finkbeiner and Eugenia M. Clérico and Richard I. Morimoto and Miguel A. Prado and Alfred C.O. Vertegaal and Kay Hofmann and Daniel J. Finley},
  journal = {Autophagy},
  year = {2026},
  month = oct,
  doi = {10.1080/15548627.2026.2741092},
  url = {https://doi.org/10.1080/15548627.2026.2741092},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Survey of the human proteostasis network: the ubiquitin-proteasome system
AU  - Suzanne Elsasser
AU  - Evan T. Powers
AU  - Thomas Stoeger
AU  - Xiaojing Sui
AU  - Roy D. Kurtzbard
AU  - Patricia Martínez-Botía
AU  - Margaret A. Wangeline
AU  - Alejandro Rodríguez Gama
AU  - Edward L. Huttlin
AU  - Lisa P. Elia
AU  - Jeffery W. Kelly
AU  - Jason E. Gestwicki
AU  - Judith Frydman
AU  - Steven M. Finkbeiner
AU  - Eugenia M. Clérico
AU  - Richard I. Morimoto
AU  - Miguel A. Prado
AU  - Alfred C.O. Vertegaal
AU  - Kay Hofmann
AU  - Daniel J. Finley
PY  - 2026
DA  - 2026/10/29
JO  - Autophagy
DO  - 10.1080/15548627.2026.2741092
UR  - https://doi.org/10.1080/15548627.2026.2741092
AB  - Modification by ubiquitination governs the half-lives of thousands of proteins that are fated for elimination by either the proteasome or autophagy pathways, depending on the intricate architectures of ubiquitin modification. This system mediates quality control for individual proteins, protein complexes, and organelles, as well as myriad purely regulatory functions. Here we provide a comprehensive survey of the ubiquitin-proteasome system (UPS), the scope of which is at present poorly defined. The UPS, with the inclusion of pathways involving ubiquitin-like modifiers, comprises in our estimate over 1430 distinct components in humans, a vast set of activities whose collective impact on the biology of the cell is pervasive. The UPS is an integral component of the proteostasis network (PN), the remainder of which is surveyed in the accompanying reports. With the addition of molecular chaperones, proteins from autophagy-lysosome pathway, and related activities, the PN includes in total over 3150 components by our estimates. Comprehensive and systematic definition of these pathways should facilitate a range of ongoing investigations in the areas of genomics, proteomics, biochemistry, cell biology, and disease research.Abbreviations: APC, anaphase promoting complex; CDD, Conserved Domain Database; CRL, cullin RING ligase; DSB, double-strand break; DUB, deubiquitinating enzyme; ERAD, ER-associated degradation; PN, proteostasis network; RBR, RING-between-RING; RCR, RING-Cys-Relay; SPOC, Structure Prediction and Omics-informed Classifier; UB, ubiquitin; UBL, ubiquitin-like; UBLM, ubiquitin-like modifier; UEV, ubiquitin-conjugating enzyme variant; UPS, ubiquitin-proteasome system
SN  - 1554-8627
SN  - 1554-8635
ER  -