Oxidative stress represents a complex and intensely studied phenomenon tightly linked to a range of human diseases, and to aging in many organisms. A plethora of key cellular regulators, including the Notch signaling pathway, have been recently described to respond to the cellular redox status. We have characterized the role of CSL (CBF1/Su(H)/LAG-1) proteins, the effectors of Notch signaling pathway in metazoa, in oxidative stress response in fission yeast. Schizosaccharomyces pombe contains two CSL paralogs, Cbf11 and Cbf12, that have antagonistic functions in the regulation of cell cycle and cellular adhesion. Both proteins are able to bind the canonical CSL motif and activate transcription and, thus, function as genuine CSL transcription factors. We have determined that the strain lacking cbf11 is resistant to hydrogen peroxide but not to menadione, a source of superoxide anion radical. Using double knock-outs to assess genetic interactions we have revealed that the resistance of cbf11 knock-out is dependent on the antioxidants catalase and sulfiredoxin. Genes encoding these antioxidants are under transcriptional control of the Sty1 MAP kinase pathway and the Pap1 transcription factor which are also required for the resistance of Δcbf11 cells. Cbf12 is believed to play only a minor role in...

Redox homeostasis maintenance is important for proper organism and cell function, for while relatively low amount of reactive oxygen (and nitrogen) species contributes to the fine tuning of signal transduction, excessive concentration of ROS (oxidative stress) has demonstrably harmful effects and is tightly connected to many pathological states. Cells therefore evolved broad palette of antioxidant mechanisms that express striking level of conservation among different species. Large, intricate stress response signaling networks have been already described; nonetheless, novel molecules employed in stress-related signaling are still being discovered. Several studies recently suggested transcription factors CSL, proteins essential for regulation of metazoan development as effectors of Notch signaling, are also involved in response to oxidative stress. The fission yeast Schizosaccharomyces pombe, well established model of response to various stresses, comprises two paralogs of CSL proteins - Cbf11 and Cbf12. We have found cells depleted of cbf11 are highly resistant to hydrogen peroxide. This resistance appears to be caused by upregulation of important stress responsive genes including ctt1, gst2, pyp2, and atf1. Cbf11 is therefore negative regulator of these genes, which suppresses their expression...