Reactive oxygen species mediated Cezanne inactivation by oxidation of its catalytic cysteine residue in hepatocellular carcinoma.

Reactive oxygen species mediated Cezanne inactivation by oxidation of its catalytic cysteine residue in hepatocellular carcinoma. Oncol Res. 2019 May 09;: Authors: Yin Z, Yang L, Wu F, Fan J, Xu J, Jin Y, Yang G Abstract Cysteine oxidation occurs at the active site of deubiquitinases (DUBs) during many biologic signaling cascades. Here we report that hepatocellular carcinoma cells (HCC) generated higher levels of endogenous reactive oxygen species (ROS). This elevated ROS production was inhibited by NADPH oxidase inhibitor diphenylene iodonium (DPI) and mitochondria electron chain inhibitor rotenone in HCC cells. Moreover, we found that H₂O₂ could activate NF-κB dependent inflammatory effect through increased induction of matrix metalloproteinase 2 (MMP2), MMP9, and intercellular adhesion molecule 1 (ICAM1) expression levels. In addition, we found that H₂O₂ could prolong NF-κB activation by suppressing the negative regulatory functions of Cezanne in HCC cells. Ubiquitin-derived thiolreactive probe (HA-UbVME) assay and biotin-tagged 1,3-cyclohexadione derivative (DCP-Bio1) assay shown that H₂O₂ has the capacity to inhibit the catalytic activity of Cezanne and reducing agent, DTT, could re-activate the Cezanne de-ubiquitinating enzyme activity. Taken all together, these findings demonstrated an important role for oxidation of Cezanne by ROS in regulation of inflammatory effect of hepatocellular carcinoma. PMID: 31...
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research