RESUMEN
Hypoxia-induced interleukin-32ß (IL-32ß) shifts the metabolic program to the enhanced glycolytic pathway. In the present study, the underlying mechanism by which hypoxia-induced IL-32ß stability is regulated was investigated in ovarian cancer cells. IL-32ß expression increased under hypoxic conditions in ovarian cancer cells as it did in breast cancer cells. The amount of IL-32ß was regulated by post-translational control rather than by transcriptional activation. Under normoxic conditions, IL-32ß was continuously eliminated through ubiquitin-dependent degradation by the von-Hippel Lindau (VHL) E3 ligase complex. Oxygen deficiency or reactive oxygen species (ROS) disrupted the interaction between IL-32ß and VHL, leading to the accumulation of the cytokine. The fact that IL-32ß is regulated by the energy-consuming ubiquitination system implies that it plays an important role in oxidative stress. We found that IL-32ß reduced protein kinase Cδ (PKCδ)-induced apoptosis under oxidative stress. This implies that the hypoxia- and ROS-stabilized IL-32ß contributes to sustain survival against PKCδ-induced apoptosis.