Retrograde regulation of multidrug resistance in Saccharomyces cerevisiae
Retrograde regulation of multidrug resistance in Saccharomyces cerevisiae
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DOI：
10.1016/j.gene.2005.03.019
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发表时间：
2005-07-18
期刊：
影响因子：
3.5
通讯作者：
Moye-Rowley, WS
中科院分区：
文献类型：
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作者：
Moye-Rowley, WS
线粒体和细胞核之间的通讯是确保细胞正确代谢协调的必要条件。从线粒体到细胞核的信号传导途径被称为逆行信号传导，最早是在酵母中发现的。缺乏线粒体基因组的细胞（rho(0)细胞）触发核CIT2基因的表达，以确保足够的氨基酸生物合成。最近，研究发现酿酒葡萄球菌多药耐药的另一组基因在rho(0)细胞中被强烈诱导。在寻找atp结合盒（ABC）转运体编码基因PDR5的负调节因子时，观察到rho(0)突变体表现出该基因转录的显著上调。这种诱导是由于PDR5的直接上游调节因子Pdr3p的翻译后激活。LGEI基因的缺失导致rho(0)介导的PDR5表达阻滞。其他人已经观察到Lge1p与泛素结合酶Rad6p和泛素连接酶Bre1p一起参与组蛋白H2B泛素化。我们的研究提供了证据，证明Lge1p具有H2B泛素化所特有的另一种功能，这种功能是PDR5转录逆行调控所必需的。我们还发现Pdr通路调节了几个参与鞘脂生物合成的基因的表达。这些发现提示PDR基因的生理作用可能是调节膜稳态，rho(0)触发的该参数的变化可能是控制PDR基因表达的信号。(c) 2005年Elsevier B.V.出版
Communication between the mitochondria and the nucleus is essential to ensure correct metabolic coordination of the cell. Signaling pathways leading from the mitochondria to the nucleus are referred to as retrograde signaling and were first discovered in the yeast Saccharomyces cerevisiae. Cells that lack their mitochondrial genome (rho(0) cells) trigger expression of the nuclear CIT2 gene in order to ensure adequate amino acid biosynthesis. More recently, it has been found that a different set of genes involved in multidrug resistance in S. cerevisiae is strongly induced in rho(0) cells. During a search for negative regulators of the ATP-binding cassette (ABC) transporter-encoding gene PDR5, it was observed that rho(0) mutants exhibited dramatic up-regulation of the transcript of this gene. This induction was due to the post-translational activation of a direct upstream regulator of PDR5 that was designated Pdr3p. Loss of the LGEI gene led to a block in rho(0)- mediated induction of PDR5 expression. Lge1p has been observed by others to be involved in histone H2B ubiquitination along with the ubiquitin-conjugating enzyme Rad6p and the ubiquitin ligase Bre1p. Our studies provide evidence that Lge1p has another function unique from H2B ubiquitination that is required for retrograde regulation of PDR5 transcription. We have also found that the Pdr pathway regulates expression of several genes involved in sphingolipid biosynthesis. These findings suggest that the physiological role of the PDR genes might be to regulate membrane homeostasis and rho(0)-triggered changes in this parameter may be the signal controlling PDR gene expression. (c) 2005 Published by Elsevier B.V.