Degradation bottlenecks and resource competition in transiently and stably engineered mammalian cells.

ABSTRACT: Degradation tags, otherwise known as degrons, are portable sequences that can be used to alter protein stability. Here, we report that degron-tagged proteins compete for cellular degradation resources in engineered mammalian cells leading to coupling of the degradation rates of otherwise independently expressed proteins when constitutively targeted human degrons are adopted. We show the effect of this competition to be dependent on the context of the degrons. By considering different proteins, degron position and cellular hosts, we highlight how the impact of the degron on both degradation strength and resource coupling changes, with identification of orthogonal combinations. By adopting inducible bacterial and plant degrons we also highlight how controlled uncoupling of synthetic construc

SUBMITTER: Gabrielli J 

PROVIDER: S-EPMC11696530 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature