A Glutathione S-Transferase Pi Molecular Glue Tethers Splicing Factors and Remodels Cell Metabolism.

ABSTRACT: Here, we discovered a tyrosine-reactive GSTP1 inhibitor can function as a molecular glue via a ligand induced protein tethering (LIPT) mechanism. Electrophilic modification of GSTP1 results in disulfide tethering of protein complexes in live cells, and these protein-protein interactions (PPIs) can be reversed using reducing agents. A substantial fraction of GSTP1 tethered interactions represent neo-PPIs that were enriched for splicing factors and nuclear proteins as determined by immunopurification mass spectrometry. LIPT colocalized GSTP1 with serine/arginine repetitive matrix protein 1 (SRRM1), resulting in its redistribution from nuclear speckles to cytoplasmic foci. Cancer cells with enhanced sensitivity to LIPT showed downregulation of metabolic proteins that led to altered lipid meta

SUBMITTER: Leace DM 

PROVIDER: S-EPMC12753042 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature