p53 regulates the mevalonate pathway in human glioblastoma multiforme.
p53 regulates the mevalonate pathway in human glioblastoma multiforme.
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p53调节人类胶质母细胞瘤多形的甲谷酸途径。
DOI：
10.1038/cddis.2015.279
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发表时间：
2015-10-15
影响因子：
9
通讯作者：
Bifulco M
中科院分区：
文献类型：
--
作者：
Laezza C;D'Alessandro A;Di Croce L;Picardi P;Ciaglia E;Pisanti S;Malfitano AM;Comegna M;Faraonio R;Gazzerro P;Bifulco M
甲羟戊酸（MVA）途径是一个重要的代谢途径，涉及肿瘤发生的多个方面。在这项研究中，我们提供了证据，证明p53诱导MVA途径的一组酶的表达，包括3 ' -羟基-3 ' -甲基戊二酰辅酶a还原酶、MVA激酶、法尼基二磷酸合成酶和法尼基二磷酸转移酶1，在人胶质母细胞瘤多形性细胞系U343细胞和正常人星形细胞NHAs中。遗传和药理学干扰p53直接影响这些基因的表达。此外，p53被招募到指定的p53应答元件的基因启动子中，从而增加了它们的转录。这种效应被基因启动子p53反应元件的定点突变所消除。这些发现突出了p53与肿瘤抑制无关的功能的另一个方面，并表明p53是MVA途径的一种新的调节剂，从而深入了解了该途径在癌症进展中的作用。
The mevalonate (MVA) pathway is an important metabolic pathway implicated in multiple aspects of tumorigenesis. In this study, we provided evidence that p53 induces the expression of a group of enzymes of the MVA pathway including 3′-hydroxy-3′-methylglutaryl-coenzyme A reductase, MVA kinase, farnesyl diphosphate synthase and farnesyl diphosphate farnesyl transferase 1, in the human glioblastoma multiforme cell line, U343 cells, and in normal human astrocytes, NHAs. Genetic and pharmacologic perturbation of p53 directly influences the expression of these genes. Furthermore, p53 is recruited to the gene promoters in designated p53-responsive elements, thereby increasing their transcription. Such effect was abolished by site-directed mutagenesis in the p53-responsive element of promoter of the genes. These findings highlight another aspect of p53 functions unrelated to tumor suppression and suggest p53 as a novel regulator of the MVA pathway providing insight into the role of this pathway in cancer progression.