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首页> 外文期刊>Molecular and Cellular Biology >Mxr1p, a Key Regulator of the Methanol Utilization Pathway and Peroxisomal Genes in Pichia pastoris
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Mxr1p, a Key Regulator of the Methanol Utilization Pathway and Peroxisomal Genes in Pichia pastoris

机译：Mxr1p，毕赤酵母中甲醇利用途径和过氧化物酶体基因的关键调控因子

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Growth of the yeast Pichia pastoris on methanol induces the expression of genes whose products are required for its metabolism. Three of the methanol pathway enzymes are located in an organelle called the peroxisome. As a result, both methanol pathway enzymes and proteins involved in peroxisome biogenesis (PEX proteins) are induced in response to this substrate. The most highly regulated of these genes is AOX1, which encodes alcohol oxidase, the first enzyme of the methanol pathway, and a peroxisomal enzyme. To elucidate the molecular mechanisms responsible for methanol regulation, we identify genes required for the expression of AOX1. Mutations in one gene, named MXR1 (methanol expression regulator 1), result in strains that are unable to (i) grow on the peroxisomal substrates methanol and oleic acid, (ii) induce the transcription of AOX1 and other methanol pathway and PEX genes, and (iii) form normal-appearing peroxisomes in response to methanol. MXR1 encodes a large protein with a zinc finger DNA-binding domain near its N terminus that has similarity to Saccharomyces cerevisiae Adr1p. In addition, Mxr1p is localized to the nucleus in cells grown on methanol or other gluconeogenic substrates. Finally, Mxr1p specifically binds to sequences upstream of AOX1. We conclude that Mxr1p is a transcription factor that is necessary for the activation of many genes in response to methanol. We propose that MXR1 is the P. pastoris homologue of S. cerevisiae ADR1 but that it has gained new functions and lost others through evolution as a result of changes in the spectrum of genes that it controls.
机译：酵母巴斯德毕赤酵母在甲醇上的生长会诱导其代谢所需产物的基因表达。三种甲醇途径酶位于称为过氧化物酶体的细胞器中。结果，响应于该底物，诱导了甲醇途径酶和过氧化物酶体生物发生中涉及的蛋白质（PEX蛋白质）。这些基因中受最严格调控的是 AOX1 ，它编码醇氧化酶，甲醇途径的第一个酶和过氧化物酶体酶。为了阐明负责甲醇调节的分子机制，我们鉴定了表达 AOX1 所需的基因。一个名为 MXR1 （甲醇表达调节剂1）的基因的突变导致菌株无法（i）在过氧化物酶体底物甲醇和油酸上生长，（ii）诱导 AOX1 和其他甲醇途径以及 PEX 基因，以及（iii）响应甲醇形成正常出现的过氧化物酶体。 MXR1 编码一个大蛋白，在其N末端附近具有一个锌指DNA结合结构域，该结构域与 Saccharomyces cerevisiae Adr1p具有相似性。此外，Mxr1p定位于在甲醇或其他糖异生底物上生长的细胞中的核。最后，Mxr1p与 AOX1 上游的序列特异性结合。我们得出结论，Mxr1p是转录因子，是激活许多基因以响应甲醇所必需的。我们建议 MXR1 是 P。 S。的pastoris 同源物。 cerevisiae ADR1 ，但是由于它控制的基因谱的变化，它通过进化获得了新功能，而失去了其他功能。

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