The ubiquitin-proteasome system and assays to determine responses to inhibitors.
Expert Opin Drug Discov
; 5(12): 1221-36, 2010 Dec.
Article
en En
| MEDLINE
| ID: mdl-22822722
IMPORTANCE OF THE FIELD: Proteasome inhibition is an important therapeutic modality. Additionally, given the toxicities of direct proteasome inhibition, interest is increasing in modulating the ubiquitin ligases in the ubiquitin-proteasome system (UPS). AREAS COVERED IN THIS REVIEW: A detailed examination of the ubiquitin-proteasome pathway and an examination of methods of inhibiting this pathway from a variety of targets including the proteasome, the ubiquitin ligases and molecular biology techniques. Special attention is given to the assays used to measure modulation of the ubiquitin-proteasome pathway. WHAT THE READER WILL GAIN: A thorough examination of the UPS and its role in cells and disease and an overview of several assays for analyzing the effect of inhibitors on the UPS. Significant detail is given to assays of the ligase system and molecular approaches. These assays have their own advantages and disadvantages and will allow investigators to make informed choices on investigating the UPS. TAKE HOME MESSAGE: Interrupting the UPS can have profound consequences for cellular health and disease progression. The ubiquitin-proteasome pathway contains multiple activities that cannot be definitively assayed by a single technique. Assaying the UPS requires investigators to use multiple corroborating techniques and avoid confounding issues within each technique.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Expert Opin Drug Discov
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido