PUBLICATION
Blue Light Activated Rapamycin for Optical Control of Protein Dimerization in Cells and Zebrafish Embryos
- Authors
- Courtney, T.M., Darrah, K.E., Horst, T.J., Tsang, M., Deiters, A.
- ID
- ZDB-PUB-211006-7
- Date
- 2021
- Source
- ACS Chemical Biology 16(11): 2434-2443 (Journal)
- Registered Authors
- Tsang, Michael
- Keywords
- none
- MeSH Terms
-
- Animals
- Dimerization
- Embryo, Nonmammalian/metabolism
- Green Fluorescent Proteins/metabolism
- HeLa Cells
- Humans
- Light*
- Proteins/metabolism*
- Sirolimus/analogs & derivatives*
- Sirolimus/radiation effects
- Subcellular Fractions/metabolism
- Zebrafish/embryology*
- PubMed
- 34609839 Full text @ ACS Chem. Biol.
Citation
Courtney, T.M., Darrah, K.E., Horst, T.J., Tsang, M., Deiters, A. (2021) Blue Light Activated Rapamycin for Optical Control of Protein Dimerization in Cells and Zebrafish Embryos. ACS Chemical Biology. 16(11):2434-2443.
Abstract
Rapamycin-induced dimerization of FKBP and FRB is the most commonly utilized chemically induced protein dimerization system. It has been extensively used to conditionally control protein localization, split-enzyme activity, and protein-protein interactions in general by simply fusing FKBP and FRB to proteins of interest. We have developed a new aminonitrobiphenylethyl caging group and applied it to the generation of a caged rapamycin analog that can be photoactivated using blue light. Importantly, the caged rapamycin analog shows minimal background activity with regard to protein dimerization and can be directly interfaced with a wide range of established (and often commercially available) FKBP/FRB systems. We have successfully demonstrated its applicability to the optical control of enzymatic function, protein stability, and protein subcellular localization. Further, we also showcased its applicability toward optical regulation of cell signaling, specifically mTOR signaling, in cells and aquatic embryos.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping