Protein Knockdown Technology: Application of Ubiquitin Ligase to Cancer Therapy
| Autor: | Nobumichi Ohoka, Mikihiko Naito, Norihito Shibata, Takayuki Hattori |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Proteasome Endopeptidase Complex Cancer Research Receptors Retinoic Acid Ubiquitin-Protein Ligases Down-Regulation Receptors Cytoplasmic and Nuclear Antineoplastic Agents Cell Cycle Proteins Ligands Inhibitor of Apoptosis Proteins 03 medical and health sciences Ubiquitin Downregulation and upregulation Leucine Neoplasms Drug Discovery Animals Humans Molecular Targeted Therapy Pharmacology Gene knockdown biology Protein Stability Ubiquitination Small molecule Neoplasm Proteins Ubiquitin ligase Cell biology Cytosol 030104 developmental biology Oncology Biochemistry Drug Design Proteolysis Cancer cell biology.protein Target protein Oligopeptides Signal Transduction |
| Zdroj: | Current Cancer Drug Targets. 16:136-146 |
| ISSN: | 1568-0096 |
| Popis: | Selective degradation of pathogenic proteins by small molecules in cells is a novel approach for development of therapeutic agents against various diseases, including cancer. We and others have developed a protein knockdown technology with a series of hybrid small compounds, called SNIPERs (Specific and Nongenetic IAP-dependent Protein ERasers); and peptidic chimeric molecules, called PROTACs (proteolysis-targeting chimeric molecules), which induce selective degradation of target proteins via the ubiquitin-proteasome pathway. These compounds include two different ligands connected by a linker; one is a ligand for a ubiquitin ligase and the other is a ligand for the target protein, which are expected to crosslink these proteins in cells. Theoretically, any cytosolic protein can be targeted for degradation by this technology. To date, several SNIPERs and PROTACs against various oncogenic proteins have been developed, which specifically induce polyubiquitylation and proteasomal degradation of the oncogenic proteins, resulting in cell death, growth arrest, or impaired migration of cancer cells. Thus, this protein knockdown technology has a great potential for cancer therapy. |
| Databáze: | OpenAIRE |
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