Pooled endogenous protein tagging and recruitment for systematic profiling of protein function.

ABSTRACT: The emerging field of induced proximity therapeutics, which involves designing molecules to bring together an effector and target protein-typically to induce target degradation-is rapidly advancing. However, its progress is constrained by the lack of scalable and unbiased tools to explore effector-target protein interactions. We combine pooled endogenous gene tagging using a ligand-binding domain with generic small-molecule-based recruitment to screen for induction of protein proximity. We apply this methodology to identify effectors for degradation in two orthogonal screens: using fluorescence to monitor target levels and a cellular growth that depends on the degradation of an essential protein. Our screens revealed new effector proteins for degradation, including previously established e

SUBMITTER: Serebrenik YV 

PROVIDER: S-EPMC11602618 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature