Back to Search
Start Over
Revealing β-TrCP activity dynamics in live cells with a genetically encoded biosensor.
Revealing β-TrCP activity dynamics in live cells with a genetically encoded biosensor.
- Source :
-
Nature communications [Nat Commun] 2022 Oct 26; Vol. 13 (1), pp. 6364. Date of Electronic Publication: 2022 Oct 26. - Publication Year :
- 2022
-
Abstract
- The F-box protein beta-transducin repeat containing protein (β-TrCP) acts as a substrate adapter for the SCF E3 ubiquitin ligase complex, plays a crucial role in cell physiology, and is often deregulated in many types of cancers. Here, we develop a fluorescent biosensor to quantitatively measure β-TrCP activity in live, single cells in real-time. We find β-TrCP remains constitutively active throughout the cell cycle and functions to maintain discreet steady-state levels of its substrates. We find no correlation between expression levels of β-TrCP and β-TrCP activity, indicating post-transcriptional regulation. A high throughput screen of small-molecules using our reporter identifies receptor-tyrosine kinase signaling as a key axis for regulating β-TrCP activity by inhibiting binding between β-TrCP and the core SCF complex. Our study introduces a method to monitor β-TrCP activity in live cells and identifies a key signaling network that regulates β-TrCP activity throughout the cell cycle.<br /> (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 36289220
- Full Text :
- https://doi.org/10.1038/s41467-022-33762-3