p53 regulates the mevalonate pathway in human glioblastoma multiforme
| Autor: | Laezza C1, D'Alessandro A2, 3, Di Croce L4, Picardi P2, Ciaglia E2, Pisanti S2, Malfitano AM2, Comegna M5, 6, Faraonio R5, Gazzerro P2, Bifulco M2 |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Cell death and disease (2015). info:cnr-pdr/source/autori:Laezza C1, D'Alessandro A2,3, Di Croce L4, Picardi P2,3, Ciaglia E2,3, Pisanti S2,3, Malfitano AM2,3, Comegna M5,6, Faraonio R5,6, Gazzerro P2,3, Bifulco M2,3./titolo:p53 regulates the mevalonate pathway in human glioblastoma multiforme./doi:/rivista:Cell death and disease/anno:2015/pagina_da:/pagina_a:/intervallo_pagine:/volume |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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