Glutathione peroxidase-1 regulates ASK1-dependent apoptosis via interaction with TRAF2 in RIPK3-negative cancer cells.

ABSTRACT: Glutathione peroxidase (GPx) is a selenocysteine-containing peroxidase enzyme that defends mammalian cells against oxidative stress, but the role of GPx signaling is poorly characterized. Here, we show that GPx type 1 (GPx1) plays a key regulatory role in the apoptosis signaling pathway. The absence of GPx1 augmented TNF-α-induced apoptosis in various RIPK3-negative cancer cells by markedly elevating the level of cytosolic H₂O₂, which is derived from mitochondria. At the molecular level, the absence of GPx1 led to the strengthened sequential activation of sustained JNK and caspase-8 expression. Two signaling mechanisms are involved in the GPx1-dependent regulation of the apoptosis pathway: (1) GPx1 regulates the level of cytosolic H₂O₂ that oxidi

SUBMITTER: Lee S 

PROVIDER: S-EPMC8257591 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature