Tripathi Gyanendra, Wiltshire Carolyn, Macaskill Susan, Tournu Helene, Budge Susan, Brown Alistair J P
Department of Molecular and Cell Biology, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK.
EMBO J. 2002 Oct 15;21(20):5448-56. doi: 10.1093/emboj/cdf507.
Candida albicans is a major fungal pathogen of humans. It regulates its morphology in response to various environmental signals, but many of these signals are poorly defined. We show that amino acid starvation induces filamentous growth in C.albicans. Also, starvation for a single amino acid (histidine) induces CaHIS4, CaHIS7, CaARO4, CaLYS1 and CaLYS2 gene expression in a manner reminiscent of the GCN response in Saccharomyces cerevisiae. These morphogenetic and GCN-like responses are both dependent upon CaGcn4, which is a functional homologue of S.cerevisiae Gcn4. Like ScGcn4, CaGcn4 activates the transcription of amino acid biosynthetic genes via the GCRE element, and CaGcn4 confers resistance to the histidine analogue, 3-aminotriazole. CaGcn4 interacts with the Ras-cAMP pathway to promote filamentous growth, but the GCN-like response is not dependent upon morphogenetic signalling. CaGcn4 acts as a global regulator in C.albicans, co-ordinating both metabolic and morphogenetic responses to amino acid starvation.
白色念珠菌是人类主要的真菌病原体。它会根据各种环境信号调节其形态,但其中许多信号的定义并不明确。我们发现氨基酸饥饿会诱导白色念珠菌形成丝状生长。此外,单一氨基酸(组氨酸)饥饿会以一种类似于酿酒酵母中GCN反应的方式诱导CaHIS4、CaHIS7、CaARO4、CaLYS1和CaLYS2基因表达。这些形态发生和类似GCN的反应都依赖于CaGcn4,它是酿酒酵母Gcn4的功能同源物。与ScGcn4一样,CaGcn4通过GCRE元件激活氨基酸生物合成基因的转录,并且CaGcn4赋予对组氨酸类似物3-氨基三唑的抗性。CaGcn4与Ras-cAMP途径相互作用以促进丝状生长,但类似GCN的反应不依赖于形态发生信号传导。CaGcn4在白色念珠菌中作为全局调节因子,协调对氨基酸饥饿的代谢和形态发生反应。