Proteolysis: from the lysosome to ubiquitin and the proteasome
Abstract
How the genetic code is translated into proteins was a key focus of biological research before the 1980s, but how these proteins are degraded remained a neglected area. With the discovery of the lysosome, it was suggested that cellular proteins are degraded in this organelle. However, several independent lines of experimental evidence strongly indicated that non-lysosomal pathways have an important role in intracellular proteolysis, although their identity and mechanisms of action remained obscure. The discovery of the ubiquitin-proteasome system resolved this enigma.
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Lysosomes contribute to the enlargement of spines through fusion and donation to dendritic membrane surface area; concurrently, extrusion of cathepsin B into extracellular space initiates a downstream cleavage cascade that promotes remodeling of the extracellular matrix.
“For example, lysosomes contribute to the enlargement of spines through fusion and thus donation to dendritic membrane surface area; concurrently, extrusion of the protease cathepsin B into the extracellular space initiates a downstream cleavage cascade that promotes remodeling of the extracellular matrix (ECM).32”
From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [32]
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- Authors
- Ciechanover, A.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- Corresponding author
- Ciechanover, Aaron
- ORCID
- Ciechanover, Aaron
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2005-01
- Volume
- 6
- Issue
- 1
- Pages
- 79-87
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W1590553747
- Cited by
- 1,133
- References
- 1
- Citations by year
- 2026: 38 · 2025: 68 · 2024: 41 · 2023: 42 · 2022: 55 · 2021: 43 · 2020: 74 · 2019: 52 · 2018: 44 · 2017: 51 · 2016: 54 · 2015: 47 · 2014: 54 · 2013: 61 · 2012: 62
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- proteolysis, lysosomes, ubiquitin, proteasome, ubiquitin-proteasome system, protein degradation
- MeSH terms
- Animals, Humans, Lysosomes, Microscopy, Electron, Proteins, Ubiquitin, Proteasome Endopeptidase Complex
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