Cited by 1,377Protease and Inhibitor MechanismsUbiquitin and proteasome pathwaysCalpain Protease Function and Regulation

Cysteine cathepsins: From structure, function and regulation to new frontiers

Open access
Turk, Vito, Stoka, Veronika, Vasiljeva, Olga, Renko, Miha, Sun, Tao, Turk, Boris, Turk, Dušan·2012·Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.bbapap.2011.10.002

Cites

368 of 368 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. [200]Barrett A.J. Rawlings N.D. Davies M.E. Machleidt W. Salvensen G. Turk V. Cysteine proteinase inhibitors of cystatin superfamily Barrett A.J. Salvesen G. Proteinase Inhibitors 1986 Elsevier Amsterdam 519 569
  2. [363]D. Turk, Weiterentwicklung eines programms fuer molekuelgraphik und elektrondichte-manipulation und seine anwendung auf verschiedene protein-strukturaufklaerungen. PhD Thesis, Technische Universität, München (1992).

Cited by

Sorted by citations

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)
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review