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Published on: March 17, 2010
Cysteine cathepsins: from structure, function and regulation to new frontiers
Vito Turk1, Veronika Stoka, Olga Vasiljeva
1Department of Biochemistry and Molecular and Structural Biology, J. Stefan Institute, Ljubljana, Slovenia. dusan.turk@ijs.si
Biochimica Et Biophysica Acta
|October 26, 2011
Summary
Cysteine cathepsins, key lysosomal proteases, are increasingly recognized for diverse roles beyond protein turnover. Their involvement in antigen presentation and diseases like cancer highlights their significance.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Medicine
Background:
- Lysosomes, discovered over 50 years ago, contain hydrolytic enzymes like cysteine cathepsins.
- Cysteine cathepsins, papain-like proteases, exhibit unique reactive sites and tissue-specific expression.
- Their activity is tightly regulated by expression, activation, inhibition, and degradation.
Purpose of the Study:
- To review recent advances in understanding cysteine cathepsins.
- To explore their diverse cellular roles and involvement in diseases.
- To highlight new research tools and therapeutic strategies.
Main Methods:
- Analysis of substrate binding sites and small-molecule inhibitors.
- Review of crystal structures for drug development.
- Examination of evidence for non-lysosomal localization and functions.
Main Results:
- Cysteine cathepsins are implicated in endosomal antigen presentation and non-lysosomal processes.
- Their roles extend to diseases such as cancer and rheumatoid arthritis.
- Nitriles are emerging as promising inhibitors, surpassing epoxysuccinyls.
Conclusions:
- Cysteine cathepsins are crucial regulators and signaling molecules in numerous biological processes.
- Identifying endogenous substrates is key to understanding their mechanisms.
- Further research promises new insights and therapeutic applications.
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