Intracellular arginine-dependent translation sensor reveals the dynamics of arginine starvation response and resistance in ASS1-negative cells.

ABSTRACT:

Background

Many cancers silence the metabolic enzyme argininosuccinate synthetase 1 (ASS1), the rate-limiting enzyme for arginine biosynthesis within the urea cycle. Consequently, ASS1-negative cells are susceptible to depletion of extracellular arginine by PEGylated arginine deiminase (ADI-PEG20), an agent currently being developed in clinical trials. As the primary mechanism of resistance to arginine depletion is re-expression of ASS1, we sought a tool to understand the temporal emergence of the resistance phenotype at the single-cell level.

Methods

A real-time, single-cell florescence biosensor was developed to monitor arginine-dependent protein translation. The versatile, protein-based sensor provides temporal information about the metabolic adaptation of cells, as it is

SUBMITTER: Rogers LC 

PROVIDER: S-EPMC7818940 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature