Peripheral Protein Quality Control as a Novel Drug Target for CFTR Stabilizer
| Autor: | Tsukasa Okiyoneda, Ryosuke Fukuda |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities Mini Review Drug target stabilizer ubiquitination 03 medical and health sciences 0302 clinical medicine Ubiquitin Pharmacology (medical) CFTR chemistry.chemical_classification Pharmacology peripheral QC biology Peripheral membrane protein lcsh:RM1-950 Limiting Potentiator respiratory system Cystic fibrosis transmembrane conductance regulator digestive system diseases Cell biology respiratory tract diseases 030104 developmental biology Enzyme lcsh:Therapeutics. Pharmacology chemistry biology.protein RFFL 030217 neurology & neurosurgery Cftr modulator |
| Zdroj: | Frontiers in Pharmacology, Vol 9 (2018) Frontiers in Pharmacology |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2018.01100/full |
| Popis: | Conformationally defective cystic fibrosis transmembrane conductance regulator (CFTR) including rescued ΔF508-CFTR is rapidly eliminated from the plasma membrane (PM) even in the presence of a CFTR corrector and potentiator, limiting the therapeutic effort of the combination therapy. CFTR elimination from the PM is determined by the conformation-dependent ubiquitination as a part of the peripheral quality control (PQC) mechanism. Recently, the molecular machineries responsible for the CFTR PQC mechanism which includes molecular chaperones and ubiquitination enzymes have been revealed. This review summarizes the molecular mechanism of the CFTR PQC and discusses the possibility that the peripheral ubiquitination mechanism becomes a novel drug target to develop the CFTR stabilizer as a novel class of CFTR modulator. |
| Databáze: | OpenAIRE |
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