A General Chemical Method to Regulate Protein Stability in the Mammalian Central Nervous System
Iwamoto, Mari ; Björklund, Tomas LU ; Lundberg, Cecilia LU
; Kirik, Deniz
LU
and Wandless, Thomas J.
(2010)
In Chemistry and Biology
17(9).
p.981-988
- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1721006
- author
- Iwamoto, Mari
; Björklund, Tomas
LU
; Lundberg, Cecilia
LU
; Kirik, Deniz
LU
and Wandless, Thomas J.
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Chemistry and Biology
- volume
- 17
- issue
- 9
- pages
- 981 - 988
- publisher
- Cell Press
- external identifiers
-
- wos:000283283200012
- scopus:77956972260
- pmid:20851347
- ISSN
- 1879-1301
- DOI
- 10.1016/j.chembiol.2010.07.009
- language
- English
- LU publication?
- yes
- id
- f2612416-f77d-4725-9fac-4e73c9473e7c (old id 1721006)
- date added to LUP
- 2016-04-01 09:50:40
- date last changed
- 2022-04-19 20:08:16
@article{f2612416-f77d-4725-9fac-4e73c9473e7c,
abstract = {{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.}},
author = {{Iwamoto, Mari and Björklund, Tomas and Lundberg, Cecilia and Kirik, Deniz and Wandless, Thomas J.}},
issn = {{1879-1301}},
language = {{eng}},
number = {{9}},
pages = {{981--988}},
publisher = {{Cell Press}},
series = {{Chemistry and Biology}},
title = {{A General Chemical Method to Regulate Protein Stability in the Mammalian Central Nervous System}},
url = {{http://dx.doi.org/10.1016/j.chembiol.2010.07.009}},
doi = {{10.1016/j.chembiol.2010.07.009}},
volume = {{17}},
year = {{2010}},
}