FUsed in sarcoma is a novel regulator of manganese superoxide dismutase gene transcription.

Aims: FUsed in sarcoma (FUS) is a multifunctional DNA/RNA-binding protein that possesses diverse roles, such as RNA splicing, RNA transport, DNA repair, translation, and transcription. The network of enzymes and processes regulated by FUS is far from being fully described. In this study, we have focused on the mechanisms of FUS-regulated manganese superoxide dismutase (MnSOD) gene transcription.

Curbing cancer's sweet tooth: is there a role for MnSOD in regulation of the Warburg effect?

Reactive oxygen species (ROS), while vital for normal cellular function, can have harmful effects on cells, leading to the development of diseases such as cancer. The Warburg effect, the shift from oxidative phosphorylation to glycolysis, even in the presence of adequate oxygen, is an important metabolic change that confers many growth and survival advantages to cancer cells. Reactive oxygen species are important regulators of the Warburg effect.

Manganese superoxide dismutase regulation and cancer.

Mitochondria are the power plants of the eukaryotic cell and the integrators of many metabolic activities and signaling pathways important for the life and death of a cell. Normal aerobic cells use oxidative phosphorylation to generate ATP, which supplies energy for metabolism. To drive ATP production, electrons are passed along the electron transport chain, with some leaking as superoxide during the process.

Manganese superoxide dismutase vs. p53: regulation of mitochondrial ROS.

Coordination of mitochondrial and nuclear activities is vital for cellular homeostasis, and many signaling molecules and transcription factors are regulated by mitochondria-derived reactive oxygen species (ROS) to carry out this interorganellar communication. The tumor suppressor p53 regulates myriad cellular functions through transcription-dependent and -independent mechanisms at both the nucleus and mitochondria. p53 affect mitochondrial ROS production, in part, by regulating the expression of the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD).

Manganese superoxide dismutase: beyond life and death.

Manganese superoxide dismutase (MnSOD) is a nuclear-encoded antioxidant enzyme that localizes to the mitochondria. Expression of MnSOD is essential for the survival of aerobic life. Transgenic mice expressing a luciferase reporter gene under the control of the human MnSOD promoter demonstrate that the level of MnSOD is reduced prior to the formation of cancer.

Nucleophosmin blocks mitochondrial localization of p53 and apoptosis.

Activation of p53 is an important mechanism in apoptosis. However, whether the presence of p53 in mitochondria plays an important role in p53-mediated apoptosis is unclear. Here, we demonstrate that overexpression of NPM (nucleophosmin) significantly suppresses 12-O-tetradecanoylphorbol 13-acetate (TPA)-mediated apoptosis, in part, by blocking the mitochondrial localization of p53.

Interactions between SIRT1 and AP-1 reveal a mechanistic insight into the growth promoting properties of alumina (Al2O3) nanoparticles in mouse skin epithelial cells.

The physicochemical properties of nanomaterials differ from those of the bulk material of the same composition. However, little is known about the underlying effects of these particles in carcinogenesis. The purpose of this study was to determine the mechanisms involved in the carcinogenic properties of nanoparticles using aluminum oxide (Al(2)O(3)/alumina) nanoparticles as the prototype.

Chronic exposure to 12-O-tetradecanoylphorbol-13-acetate represses sod2 induction in vivo: the negative role of p50.

It is well documented that the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) can activate manganese superoxide dismutase (MnSOD) expression. However, it is unclear how repeated exposure to TPA following a single application of tumor initiator 7,12-dimethylbenz-(a)-anthracene causes tumor development. We generated transgenic mice expressing human MnSOD promoter- and enhancer-driven luciferase reporter gene and used a non-invasive imaging system to investigate the effects of TPA on MnSOD expression in vivo.

Specificity protein 1-dependent p53-mediated suppression of human manganese superoxide dismutase gene expression.

Manganese superoxide dismutase (MnSOD) is a primary antioxidant enzyme necessary for the survival of aerobic life. Previously, we demonstrated that specificity protein 1 (Sp1) is essential for the basal transcription of the MnSOD gene. We also identified nucleophosmin (NPM), an RNA-binding protein, as an important co-activator of NF-kappaB in the induction of MnSOD by cytokine and tumor promoter.