Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Virulence. 2010 Jan-Feb;1(1):45-8. doi: 10.4161/viru.1.1.10320.
Hsp90 is environmentally contingent molecular chaperone that influences the form and function of diverse signal transducers. Here we discuss our recent findings that Hsp90 regulates the morphogenetic transition from yeast to filamentous forms required for virulence of the most prevalent fungal pathogen of humans, Candida albicans, and does so via cAMP-PKA signalling. This transition is normally regulated by environmental cues that are contingent upon elevated temperature to relieve Hsp90-mediated repression of the morphogenetic program. Intriguingly, Hsp90 inhibition induces filamentation independent of the canonical PKA transcription factor Efg1, in striking similarity to a select set of morphogenetic stimuli. Further investigation will determine the downstream transcription factors through which Hsp90 regulates morphogenesis and the precise mechanism of Hsp90's interaction with the cAMP-PKA pathway. C. albicans is one of many fungal species that undergo a morphological transition in a temperature-dependent manner, thus Hsp90's capacity to govern this key developmental program may provide insight into morphogenesis of diverse organisms.
Hsp90 是一种环境依赖的分子伴侣，它影响多种信号转导物的形态和功能。在这里，我们讨论了最近的发现，即 Hsp90 通过 cAMP-PKA 信号通路调节从酵母到丝状形态的形态发生转变，这是人类最常见的真菌病原体白色念珠菌毒力所必需的。这种转变通常受到环境线索的调节，这些环境线索取决于高温以缓解 Hsp90 对形态发生程序的抑制。有趣的是，Hsp90 的抑制诱导了丝状形成，而不依赖于经典的 PKA 转录因子 Efg1，与一组特定的形态发生刺激非常相似。进一步的研究将确定 Hsp90 通过哪些下游转录因子调节形态发生以及 Hsp90 与 cAMP-PKA 途径相互作用的确切机制。白色念珠菌是许多以温度依赖性方式经历形态转变的真菌物种之一，因此 Hsp90 控制这一关键发育程序的能力可能为不同生物体的形态发生提供了见解。
