Cysteine cathepsins: From structure, function and regulation to new frontiers
Open accessAbstract
It is more than 50 years since the lysosome was discovered. Since then its hydrolytic machinery, including proteases and other hydrolases, has been fairly well identified and characterized. Among these are the cysteine cathepsins, members of the family of papain-like cysteine proteases. They have unique reactive-site properties and an uneven tissue-specific expression pattern. In living organisms their activity is a delicate balance of expression, targeting, zymogen activation, inhibition by protein inhibitors and degradation. The specificity of their substrate binding sites, small-molecule inhibitor repertoire and crystal structures are providing new tools for research and development. Their unique reactive-site properties have made it possible to confine the targets simply by the use of appropriate reactive groups. The epoxysuccinyls still dominate the field, but now nitriles seem to be the most appropriate "warhead". The view of cysteine cathepsins as lysosomal proteases is changing as there is now clear evidence of their localization in other cellular compartments. Besides being involved in protein turnover, they build an important part of the endosomal antigen presentation. Together with the growing number of non-endosomal roles of cysteine cathepsins is growing also the knowledge of their involvement in diseases such as cancer and rheumatoid arthritis, among others. Finally, cysteine cathepsins are important regulators and signaling molecules of an unimaginable number of biological processes. The current challenge is to identify their endogenous substrates, in order to gain an insight into the mechanisms of substrate degradation and processing. In this review, some of the remarkable advances that have taken place in the past decade are presented. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.
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Cancer patients have higher levels of cathepsin B protein and activity.
“However, studies have indicated that cancer patients have higher levels of its protein and activity.146”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [146]
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Comprehensive search for cysteine cathepsins in the human genome
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Kinetics of the pH-induced inactivation of human cathepsin L
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Thyropins--new structurally related proteinase inhibitors.
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Inhibition of bone resrption by selctive inactivators of cysteine proteinases
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- [363]D. Turk, Weiterentwicklung eines programms fuer molekuelgraphik und elektrondichte-manipulation und seine anwendung auf verschiedene protein-strukturaufklaerungen. PhD Thesis, Technische Universität, München (1992).
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Running-induced systemic cathepsin B secretion is associated with memory function
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- Authors
- Turk, V., Stoka, V., Vasiljeva, O., Renko, M., Sun, T., Turk, B., & Turk, D.
- Affiliations
- Jožef Stefan Institute (SI)
- Corresponding author
- Turk, Dušan
- Venue
- Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 1824
- Issue
- 1
- Pages
- 68-88
- ISSN
- 1570-9639 (ISSN-L)
- PMC
- PMC7105208
- OpenAlex
- W2075729810
- Cited by
- 1,377
- References
- 368
- Citations by year
- 2026: 93 · 2025: 104 · 2024: 96 · 2023: 96 · 2022: 95 · 2021: 111 · 2020: 147 · 2019: 113 · 2018: 108 · 2017: 101 · 2016: 93 · 2015: 84 · 2014: 63 · 2013: 43 · 2012: 30
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Slovene Research Agency (J1-2307, P1-0048, J1-9520, J3-2258, P1-0140, J1-3602)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Calpain Protease Function and Regulation
- Keywords
- cysteine cathepsins, papain-like cysteine protease, lysosomal proteases, zymogen activation, protein inhibitors, small molecule inhibitors, crystal structure, cancer, rheumatoid arthritis, substrate specificity, protein turnover
- MeSH terms
- Amino Acid Sequence, Animals, Cathepsins, Cell Biology, Humans, Models, Biological, Models, Molecular, Molecular Sequence Data, Protein Conformation, Structure-Activity Relationship, Gene Expression Regulation, Enzymologic, Sequence Homology, Amino Acid, Cysteine Proteases
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