Norstictic Acid Is a Selective Allosteric Transcriptional Regulator.

ABSTRACT: Inhibitors of transcriptional protein-protein interactions (PPIs) have high value both as tools and for therapeutic applications. The PPI network mediated by the transcriptional coactivator Med25, for example, regulates stress-response and motility pathways, and dysregulation of the PPI networks contributes to oncogenesis and metastasis. The canonical transcription factor binding sites within Med25 are large (∼900 Ų) and have little topology, and thus, they do not present an array of attractive small-molecule binding sites for inhibitor discovery. Here we demonstrate that the depsidone natural product norstictic acid functions through an alternative binding site to block Med25-transcriptional activator PPIs in vitro and in cell culture. Norstictic acid targets a binding site co

SUBMITTER: Garlick JM 

PROVIDER: S-EPMC8717358 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature