Survey of the human proteostasis network: the ubiquitin-proteasome system
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 1400 distinct proteins 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 we have also surveyed in recent studies. With the addition of molecular chaperones, proteins from autophagy-lysosome pathway, and related activities, the PN includes in total over 3100 components by our estimates. Comprehensive and systematic definition of these pathways should support a range of ongoing investigations in the areas of genomics, proteomics, biochemistry, cell biology, and disease research.
Authors
- Lisa Elia
- Richard I. Morimoto (ORCID: https://orcid.org/0000-0002-3431-445X)
- Thomas Stoeger (ORCID: https://orcid.org/0000-0002-5540-4278)
- Eugenia M. Clérico (ORCID: https://orcid.org/0000-0002-4433-8842)
- Patricia Martínez-Botía (ORCID: https://orcid.org/0000-0002-9778-5945)
- Miguel A. Prado (ORCID: https://orcid.org/0000-0002-4914-1619)
- Alejandro Rodríguez Gama (ORCID: https://orcid.org/0000-0003-3257-5549)
- Edward L. Huttlin (ORCID: https://orcid.org/0000-0002-1822-1173)
- Evan T. Powers (ORCID: https://orcid.org/0000-0001-8185-8487)
- Suzanne Elsasser (ORCID: https://orcid.org/0000-0002-0544-9726)
- Jeffery W. Kelly (ORCID: https://orcid.org/0000-0001-8943-3395)
- Dan Finley
- Roy Kurtzbard
- Alfred C.O. Vertegaal
- Jason E Gestwicki
- Xiaojing Sui
- Margaret A. Wangaline
- Judith E Frydman
- Steve Finkbeiner
- Kay Hofmann
Institutions
- Northwestern University (US)
- Scripps Research Institute (US)
- Gladstone Institutes (US)
- Harvard University (US)
- German Sport University Cologne (DE)
- University of California, San Francisco (US)
- University of Cologne (DE)
- University of Cambridge (GB)
- Leiden University Medical Center (NL)
- Northwestern University (PH)
- Simons Foundation (US)
- Rice Institute (US)
- Pediatrics and Genetics (US)
- Northwestern Medicine (US)
- Taube Koret Center (US)
- MRC Toxicology Unit (GB)
- Instituto de Investigación Sanitaria del Principado de Asturias (ES)
- Stanford University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-03-16
- DOI
- https://doi.org/10.64898/2026.03.13.711689
- Primary Topic
- Ubiquitin and proteasome pathways
- Type
- article
- Field-Weighted Citation Impact
- 0.00