Abstract
Biomolecule metabolism produces ROS (reactive oxygen species) under physiological and pathophysiological conditions. Dietary factors (alcohol) and carcinogens (EGF, DEN, and MNNG) also induce the release of ROS. ROS often causes cell stress and tissue injury, eventually resulting in disorders or diseases of the body through different signaling pathways. Normal metabolism of protein is critically important to maintain cellular function and body health. Brf1 (transcript factor II B-related factor 1) and its target genes, RNA Pol III genes (RNA polymerase III-dependent genes), control the process of protein synthesis. Studies have demonstrated that the deregulation of Brf1 and its target genes is tightly linked to cell proliferation, cell transformation, tumor development, and human cancers, while alcohol, EGF, DEN, and MNNG are able to induce the deregulation of these genes through different signaling pathways. Therefore, it is very important to emphasize the roles of these signaling events mediating the processes of Brf1 and RNA Pol III gene transcription. In the present paper, we mainly summarize our studies on signaling events which mediate the deregulation of these genes in the past dozen years. These studies indicate that Brf1 and RNA Pol III genes are novel biological targets of ROS.
Highlights
Under physiological and pathophysiological conditions, the synthesis and metabolism of biomolecules in vivo often produce ROS, which reversibly or irreversibly induces cellular stress
Our study has demonstrated that alcohol treatment of breast cancer cells enhances the activity of the ERα promoter and increases the cellular levels of ERα mRNA and protein [4], while alcohol-induced RNA Pol III gene transcription in ER+ breast cancer cell lines is much higher than that in ER- cells [4, 5]
ROS causes cellular phenotypic alterations, such as cell death, stress, apoptosis, cell proliferation, transformation, and eventually tumor development through different signaling pathways which mediate the deregulation of Brf1 and Pol III gene transcription (Figure 3), whereas the deregulation of these genes is tightly linked to the alteration of these cellular phenotypes
Summary
Under physiological and pathophysiological conditions, the synthesis and metabolism of biomolecules in vivo often produce ROS (reactive oxygen species), which reversibly or irreversibly induces cellular stress This may further affect cell growth, proliferation and transformation and even lead to tumor development. The changes result in the deregulation of Brf and Pol III genes through different signaling molecules to promote cell proliferation, cell transformation, and tumor development [4, 5, 7, 8]. As the deregulation of Brf and Pol III genes is tightly associated with cell proliferation, cell transformation, and cancer development, summarizing these signaling events and analyzing the underlying molecular mechanisms will benefit developing specific inhibitors to prevent cancer development in humans
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