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Sterol Regulatory Element Binding Proteins In Fungi: Hypoxic Transcription Factors Linked To Pathogenesis

Clara M. Bien, Peter J. Espenshade

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ABSTRACT Sterol regulatory element binding proteins (SREBPs) are membrane-bound transcription factors whose proteolytic activation is controlled by the cellular sterol concentration. Mammalian SREBPs are activated in cholesterol-depleted cells and serve to regulate cellular lipid homeostasis. Recent work demonstrates that SREBP is functionally conserved in fungi. While the ability to respond to sterols is conserved, fungal SREBPs are hypoxic transcription factors required for adaptation to a low-oxygen environment. In the fission yeast Schizosaccharomyces pombe , oxygen regulates the SREBP homolog Sre1 by independently controlling both its proteolytic activation and its degradation. SREBP is also required for adaptation to hypoxia in the human pathogens Cryptococcus neoformans and Aspergillus fumigatus . In these organisms, SREBP is required for virulence and resistance to antifungal drugs, making the SREBP pathway a potential target for antifungal therapy.