title: p53 regulates the mevalonate pathway in human glioblastoma multiforme.
abstract: 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.
authors.affiliation: Institute of Endocrinology and Experimental Oncology, IEOS CNR, Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Laezza
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.|Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: D'Alessandro
authors.affiliation: Centre de Regulacio Genomica (CRG), Universitat Pompeu Fabra, Dr. Aiguader 88, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Di Croce
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.|Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Picardi
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.|Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ciaglia
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.|Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Pisanti
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.|Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Malfitano
authors.affiliation: Department Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II' via S. Pansini, 5, Naples, Italy.|CEINGE, Biotecnologie Avanzate, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Comegna
authors.affiliation: Department Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II' via S. Pansini, 5, Naples, Italy.|CEINGE, Biotecnologie Avanzate, Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Faraonio
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.|Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Gazzerro
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.|Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bifulco
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D053858:Metabolic Networks and Pathways; D008798:Mevalonic Acid / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002784:Cholesterol; D008798:Mevalonic Acid