Targeting ubiquitin specific proteases for drug discovery
Laurent Daviet1, Frédéric Colland
1Hybrigenics SA, 3-5 Impasse Reille, 75014 Paris, France.
Biochimie
|October 27, 2007
Summary
The ubiquitin-proteasome system is crucial in diseases. Targeting upstream ubiquitin specific proteases (USPs) offers a novel strategy for developing specific, less toxic anticancer drugs.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- The ubiquitin-proteasome system (UPS) is implicated in various human diseases, including cancer.
- Proteasome inhibitors like bortezomib are approved cancer treatments, validating the UPS as a therapeutic target.
- Targeting upstream components of the UPS may yield more specific and less toxic anticancer agents.
Purpose of the Study:
- To review ubiquitin specific proteases (USPs) as potential therapeutic targets.
- To explore the role of USPs in disease pathogenesis and drug discovery.
- To bridge the gap from target validation to small molecule drug discovery for USPs.
Main Methods:
- Literature review of ubiquitin specific proteases (USPs).
- Analysis of USP involvement in disease pathways.
- Evaluation of USP as a drug target for small molecule development.
Main Results:
- Deregulation of the UPS is linked to numerous human diseases.
- Ubiquitin specific proteases (USPs) are key de-ubiquitinating enzymes.
- USPs offer a promising avenue for developing targeted therapies.
Conclusions:
- Ubiquitin specific proteases (USPs) represent a viable target for pharmacological intervention.
- Targeting USPs could lead to the development of novel anticancer drugs with improved specificity and reduced toxicity.
- Further research into USP-targeted drug discovery is warranted.
Related Concept Videos
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Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
01:13The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
02:58Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
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01:17The Proteasome Structure
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The proteasome is an...
The proteasome is an...
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These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
01:26Targets for Drug Action: Overview
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Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...