title: Initial studies to define the physiologic role of cN-II.
abstract: IMP preferring cytosolic 5'-nucleotidase II (cN-II) is a widespread enzyme whose amino acid sequence is highly conserved among vertebrates. Fluctuations of its activity have been reported in some pathological conditions and its mRNA levels have been proposed as a prognostic factor for poor outcome in patients with adult acute myeloid leukemia. As a member of the oxypurine cycle, cN-II is involved in the regulation of intracellular concentration of 5'-inosine monophosphate (IMP), 5'-guanosine monophosphate (GMP), and also 5-phosphoribose 1-pyrophosphate (PRPP) and is therefore involved in the regulation of purine and pyrimidine de novo and salvage synthesis. In addition, several studies demonstrated the involvement of cN-II in pro-drug metabolism. Notwithstanding some publications indicating that cN-II is essential for the survival of several cell types, its role in cell metabolism remains uncertain. To address this issue, we built two eucaryotic cellular models characterized by different cN-II expression levels: a constitutive cN-II knockdown in the astrocytoma cell line (ADF) by short hairpin RNA (shRNA) strategy and a cN-II expression in the diploid strain RS112 of Saccharomyces cerevisiae. Preliminary results suggest that cN-II is essential for cell viability, probably because it is directly involved in the regulation of nucleotide pools. These two experimental approaches could be very useful for the design of a personalized chemotherapy.
authors: Dipartimento di Biologia, Università di Pisa, Pisa, Italy.
authors: Daniela Nicole
authors: DN
authors: Filoni
authors: Rossana
authors: R
authors: Pesi
authors: Maria Giovanna
authors: MG
authors: Careddu
authors: Marcella
authors: M
authors: Camici
authors: Simone
authors: S
authors: Allegrini
authors: Anita
authors: A
authors: Collavoli
authors: Ilaria
authors: I
authors: Scarfone
authors: Francesca
authors: F
authors: Zucchi
authors: Alvaro
authors: A
authors: Galli
authors: Maria Grazia
authors: MG
authors: Tozzi
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism*; D001254:Astrocytoma / Q000201:enzymology / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: D012333:RNA, Messenger; D015720:5'-Nucleotidase