Bien Clara M, Espenshade Peter J
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Eukaryot Cell. 2010 Mar;9(3):352-9. doi: 10.1128/EC.00358-09. Epub 2010 Jan 29.
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.
固醇调节元件结合蛋白（SREBPs）是膜结合转录因子，其蛋白水解激活受细胞固醇浓度控制。哺乳动物SREBPs在胆固醇缺乏的细胞中被激活，用于调节细胞脂质稳态。最近的研究表明，SREBP在真菌中功能保守。虽然对固醇的反应能力是保守的，但真菌SREBPs是适应低氧环境所需的缺氧转录因子。在裂殖酵母粟酒裂殖酵母中，氧气通过独立控制其蛋白水解激活和降解来调节SREBP同源物Sre1。在人类病原体新型隐球菌和烟曲霉中，适应缺氧也需要SREBP。在这些生物体中，SREBP是毒力和抗真菌药物抗性所必需的，这使得SREBP途径成为抗真菌治疗的潜在靶点。
