A General Chemical Method to Regulate Protein Stability in the Mammalian Central Nervous System
Författare
Summary, in English
The ability to make specific perturbations to biological molecules in a cell or organism is a central experimental strategy in modern research biology. We have developed a general technique in which the stability of a specific protein is regulated by a cell-permeable small molecule. Mutants of the Escherichia coil dihydrofolate reductase (ecDHFR) were engineered to be degraded, and, when this destabilizing domain is fused to a protein of interest, its instability is conferred to the fused protein resulting in rapid degradation of the entire fusion protein. A small-molecule ligand trimethoprim (TMP) stabilizes the destabilizing domain in a rapid, reversible, and dose-dependent manner, and protein levels in the absence of TMP are barely detectable. The ability of TMP to cross the blood-brain barrier enables the tunable regulation of proteins expressed in the mammalian central nervous system.
Avdelning/ar
Publiceringsår
2010
Språk
Engelska
Sidor
981-988
Publikation/Tidskrift/Serie
Chemistry and Biology
Volym
17
Issue
9
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Cell Press
Ämne
- Neurosciences
Status
Published
Forskningsgrupp
- Brain Repair and Imaging in Neural Systems (BRAINS)
- CNS Gene Therapy
ISBN/ISSN/Övrigt
- ISSN: 1879-1301