Distinct phases of cellular signaling revealed by time-resolved protein synthesis.
| Autor: | Lee G; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA., Muir TW; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA. |
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| Jazyk: | angličtina |
| Zdroj: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Jul 10. Date of Electronic Publication: 2023 Jul 10. |
| DOI: | 10.1101/2023.07.10.548208 |
| Abstrakt: | The post-translational regulation of protein function is involved in most cellular processes. As such, synthetic biology tools that operate at this level provide opportunities for manipulating cellular states. Here, we deploy a proximity-triggered protein trans-splicing technology to enable the time-resolved synthesis of target proteins from pre-made parts. The modularity of the strategy allows for the addition or removal of various control elements as a function of the splicing reaction, in the process permitting the cellular location and/or activity state of starting materials and products to be differentiated. The approach is applied to a diverse set of proteins, including the kinase oncofusions BCR/ABL and DNAJB1/PRKACA where dynamic cellular phosphorylation events are dissected, revealing distinct phases of signaling and identifying molecular players connecting the oncofusion to cancer transformation as novel therapeutic targets of cancer cells. We envision that the tools and control strategies developed herein will allow the activity of both naturally occurring and designer proteins to be harnessed for basic and applied research. Competing Interests: Competing interests Authors declare that they have no competing interests. |
| Databáze: | MEDLINE |
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