Isopeptidases in anticancer therapy: looking for inhibitors
Andrea Sgorbissa1, Harish Potu, Claudio Brancolini
1Department of Biomedical Sciences and Technologies (DSTB), University of Udine P.le Kolbe 4 3100 Udine, Italy.
American Journal of Translational Research
|July 1, 2010
Summary
Ubiquitin modification is crucial for cell function and is altered in tumors. Isopeptidases, which remove ubiquitin, are key targets for cancer therapy due to their role in regulating oncogenes and tumor suppressors.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Ubiquitin (Ub) and ubiquitin-like (Ubl) protein post-translation modification (PTM) regulates fundamental cellular processes.
- Dysregulation of Ub/Ubl PTM turnover is implicated in tumorigenesis, affecting oncogene and tumor suppressor gene activity.
Purpose of the Study:
- To review the role of isopeptidases in the Ub/Ubl conjugation/deconjugation cycle.
- To highlight the therapeutic potential of isopeptidase inhibitors, focusing on their pro-apoptotic activities.
Main Methods:
- Literature review focusing on isopeptidases and their inhibitors.
- Analysis of the enzymatic mechanisms and regulatory roles of isopeptidases.
- Examination of the pro-apoptotic effects of identified isopeptidase inhibitors.
Main Results:
- Isopeptidases are critical deconjugating enzymes that antagonize E3 ligases in the Ub/Ubl system.
- Inhibitors of isopeptidases have demonstrated significant pro-apoptotic activities.
- Targeting isopeptidases offers a promising therapeutic strategy for cancer treatment.
Conclusions:
- Isopeptidases play a vital role in cellular homeostasis and cancer development.
- Inhibitors targeting isopeptidases represent a potential avenue for novel anti-cancer therapeutics due to their ability to induce apoptosis.
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