A light-resuming strategy as a screening method for selecting Sec61 inhibitors down-modulating PD-L1 expression.

ABSTRACT: The perturbation of protein translocation into the secretory pathway using Sec61 translocon inhibitors is a novel and promising strategy for tackling many pathological situations, including cancer and viral infections. However, a highly sensitive and direct screening platform for selecting Sec61 inhibitors is unavailable. Here, we develop a "resuming luminescence upon translocation interference" (RELITE) assay capable of selecting Sec61 inhibitors in a single round of screening. This assay exploits the inactivation of firefly luciferase, once translocated into the endoplasmic reticulum (ER), and the possibility of diverting and "re-lighting" luciferase into the cytosol by a Sec61 inhibitor. Using this method, we select small molecules capable of hampering the protein expression of the PD-L

SUBMITTER: Vitale F 

PROVIDER: S-EPMC12328631 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature