From the Department of Biochemistry, Indian Institute of Science, Bangalore 60012, India.
From the Department of Biochemistry, Indian Institute of Science, Bangalore 60012, India
J Biol Chem. 2018 Oct 26;293(43):16647-16660. doi: 10.1074/jbc.RA118.004486. Epub 2018 Sep 5.
Rtg1p and Rtg3p are two basic helix-loop-helix, retrograde transcription factors in the budding yeast Both factors heterodimerize to activate the transcription of nuclear genes in response to mitochondrial dysfunction and glutamate auxotrophy, but are not well characterized in other yeasts. Here, we demonstrate that the Rtg1p/Rtg3p-mediated retrograde signaling pathway is absent in the methylotrophic yeast We observed that Rtg1p (PpRtg1p) heterodimerizes with Rtg3p and functions as a nuclear, retrograde transcription factor in , but not in We noted that Rtg3p lacks a functional leucine zipper and interacts with neither Rtg1p (ScRtg1p) nor PpRtg1p. In the absence of an interaction with Rtg3p, PpRtg1p has apparently acquired a novel function as a cytosolic regulator of multiple metabolic pathways, including biosynthesis of glutamate dehydrogenase 2 and phosphoenolpyruvate carboxykinase required for the utilization of glutamate as the sole carbon source. PpRtg1p also had an essential role in methanol metabolism and regulated alcohol oxidase synthesis and was required for the metabolism of ethanol, acetate, and oleic acid, but not of glucose and glycerol. Although PpRtg1p could functionally complement ScRtg1p, ScRtg1p could not complement PpRtg1p, indicating that ScRtg1p is not a functional PpRtg1p homolog. Thus, PpRtg1p functions as a nuclear, retrograde transcription factor in and as a cytosolic, post-transcriptional regulator in We conclude that PpRtg1p is a key component of a signaling pathway that regulates multiple metabolic processes in .
Rtg1p 和 Rtg3p 是芽殖酵母中两种基本的螺旋-环-螺旋、逆行转录因子。这两种因子形成异二聚体，以响应线粒体功能障碍和谷氨酸营养缺陷激活核基因的转录，但在其他酵母中尚未得到很好的表征。在这里，我们证明甲基营养酵母中不存在 Rtg1p/Rtg3p 介导的逆行信号通路。我们观察到 Rtg1p（PpRtg1p）与 Rtg3p 异二聚化，并在 中作为核逆行转录因子发挥作用，但在 中不起作用。我们注意到 Rtg3p 缺乏功能性亮氨酸拉链，既不与 Rtg1p（ScRtg1p）也不与 PpRtg1p 相互作用。在与 Rtg3p 没有相互作用的情况下，PpRtg1p 显然获得了作为多种代谢途径的细胞质调节剂的新功能，包括谷氨酸脱氢酶 2 和磷酸烯醇丙酮酸羧激酶的生物合成，这些酶是利用谷氨酸作为唯一碳源所必需的。PpRtg1p 还在甲醇代谢中具有重要作用，调节醇氧化酶的合成，并需要代谢乙醇、醋酸盐和油酸，但不需要葡萄糖和甘油。尽管 PpRtg1p 可以在功能上补充 ScRtg1p，但 ScRtg1p 不能补充 PpRtg1p，表明 ScRtg1p 不是功能性 PpRtg1p 同源物。因此，PpRtg1p 在 中作为核逆行转录因子发挥作用，在 中作为细胞质转录后调节剂发挥作用。我们得出结论，PpRtg1p 是调节 中多种代谢过程的信号通路的关键组成部分。
