The deubiquitinase Usp27x as a novel regulator of cFLIP_L protein expression and sensitizer to death-receptor-induced apoptosis.

ABSTRACT: Death receptors are transmembrane proteins that can induce the activation of caspase-8 upon ligand binding, initiating apoptosis. Recent work has highlighted the great molecular complexity of death receptor signalling, in particular through ubiquitination/deubiquitination. We have earlier defined the deubiquitinase Ubiquitin-Specific Protease 27x (Usp27x) as an enzyme capable of stabilizing the pro-apoptotic Bcl-2 family member Bim. Here, we report that enhanced expression of Usp27x in human melanoma cells leads to the loss of cellular FLICE-like inhibitory protein (cFLIP) and sensitizes to Tumor necrosis factor receptor 1 (TNF-R1) or Toll-like receptor 3 (TLR3)-induced extrinsic apoptosis through enabling enhanced processing of caspase-8. The loss of cFLIP_L upon overexpression

SUBMITTER: Dold MN 

PROVIDER: S-EPMC8863773 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature