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The molecular mechanism of CSL protein participation in oxidative stress response in Schizosaccharomyces pombe
Daněk, Petr ; Převorovský, Martin (advisor) ; Sipiczki, Matthias (referee)
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...
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