Sitcheran R, Emter R, Kralli A, Yamamoto K R
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 91413-0450, USA.
Genetics. 2000 Nov;156(3):963-72. doi: 10.1093/genetics/156.3.963.
To find novel components in the glucocorticoid signal transduction pathway, we performed a yeast genetic screen to identify ligand-effect modulators (LEMs), proteins that modulate the cellular response to hormone. We isolated several mutants that conferred increased glucocorticoid receptor (GR) activity in response to dexamethasone and analyzed two of them in detail. These studies identify two genes, LEM3 and LEM4, which correspond to YNL323w and ERG6, respectively. LEM3 is a putative transmembrane protein of unknown function, and ERG6 is a methyltransferase in the ergosterol biosynthetic pathway. Analysis of null mutants indicates that LEM3 and ERG6 act at different steps in the GR signal transduction pathway.
为了在糖皮质激素信号转导途径中找到新的组分,我们进行了一项酵母遗传筛选以鉴定配体效应调节剂(LEM),即调节细胞对激素反应的蛋白质。我们分离出了几个在对地塞米松的反应中赋予糖皮质激素受体(GR)活性增加的突变体,并对其中两个进行了详细分析。这些研究鉴定出了两个基因,LEM3和LEM4,它们分别对应于YNL323w和ERG6。LEM3是一种功能未知的假定跨膜蛋白,而ERG6是麦角固醇生物合成途径中的一种甲基转移酶。对缺失突变体的分析表明,LEM3和ERG6在GR信号转导途径的不同步骤发挥作用。