Tumor necrosis factor related apoptosis inducing ligand (TRAIL) regulates deubiquitinase USP5 in tumor cells.

ABSTRACT: The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway has emerged as a cancer therapeutic target. However, clinical trials have proven that most human cancers are resistant to TRAIL. We show that exposure to recombinant TRAIL resulted in the accumulation of ubiquitinated proteins and free ubiquitin polymers, suggesting a link between TRAIL and the ubiquitin (Ub)-proteasome pathway. TRAIL treatment in cancer cells reduced the activity and cleavage of USP5, a deubiquitinase (DUB) previously shown to target unanchored Ub polymers and regulate p53-mediated transcription. TRAIL was effective in suppressing USP5 activity and cleavage in TRAIL-sensitive cells but not resistant cells. Knockdown of USP5 in TRAIL-resistant cells demonstrated that USP5 controls apoptotic respons

SUBMITTER: Potu H 

PROVIDER: S-EPMC6791380 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature