Abstract:

Reactive oxygen species （ROS） mainly comprised of super oxide, hydrogen peroxide and hydroxyl free radicals, are the side products of cell metabolism. The level of ROS brings complex impacts on cell fate, leading to complex impacts on the occurrence and progression of the oxidative stress-related human diseases such as cancer, diabetes, and neurodegeneration, but the underlying mechanism remain to be clarified. Our research group aimed in elucidating the mechanisms how different levels of ROS affect the biological events and the fate of cells, i.e. the regulatory role of ROS in signaling determining cell proliferation, differentiation and apoptosis. We specifically focus on the signaling role of ROS-regulated post-translational modifications of proteins, e.g. oxidation, ubiquitination and SUMOylation, and their links to formation, progression and remedy of cancers. Our major findings are: ①The sensitivity of cancer cells to arsenic trioxide, cisplatin and doxorubicin and other apoptosis-inducing drugs is positively correlated to the inherent cellular level of ROS. The increase of ROS level by using emodin and some other compounds, or enforced expression of Nox to cause severe oxidative stress can sensitize the apoptotic susceptibility of leukemic cells and solid tumor cells. The underlying mechanisms involve in an inhibition of RhoA, HIF-1, NF-κB and other pro-survival signaling pathways, and simultaneously an activation of caspase 9 by ROS. ②The mild oxidative stress existed in cancer cells promotes cancer genesis and progression, which may be via an induction of SENP3 to regulate the profiles of protein SUMOylation and gene expression. We ascertained for the first time that SUMO protease SENP3 is a redox sensing protein. Being induced by ROS, it is rapidly accumulated and thus regulates the sUMOylation status of a number of substrates in the nucleus, such as p300, PML and p53, leading to an adaptation of cancer cells to stressful environment and the more malignant phenotypes including survival, proliferation, angiogenesis and so on. Under this research direction we have dozens of paper published on the international journals and dozen of projects funded by NCSF. The academic achievement in this study is awarded by The Second Place Prize of The Education Ministry for Natural Science at 2011.

Key words: reactive oxygen species, oxidative stress, oxidative modification, small ubiquitin-like modifiers, cancer