title: The c-Myc target gene Rcl (C6orf108) encodes a novel enzyme, deoxynucleoside 5'-monophosphate N-glycosidase.
abstract: RCL is a c-Myc target with tumorigenic potential. Genome annotation predicted that RCL belonged to the N-deoxyribosyltransferase family. However, its putative relationship to this class of enzymes did not lead to its precise biochemical function. The purified native or N-terminal His-tagged recombinant rat RCL protein expressed in Escherichia coli exhibits the same enzyme activity, deoxynucleoside 5'-monophosphate N-glycosidase, never before described. dGMP appears to be the best substrate. RCL opens a new route in the nucleotide catabolic pathways by cleaving the N-glycosidic bond of deoxynucleoside 5'-monophosphates to yield two reaction products, deoxyribose 5-phosphate and purine or pyrimidine base. Biochemical studies show marked differences in the terms of the structure and catalytic mechanism between RCL and of its closest enzyme family neighbor, N-deoxyribosyltransferase. The reaction products of this novel enzyme activity have been implicated in purine or pyrimidine salvage, glycolysis, and angiogenesis, and hence are all highly relevant for tumorigenesis.
authors.affiliation: Unité de Chimie Organique, CNRS Unité de Recherche Associée 2128, Institut Pasteur, 25-28 Rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: Yoan Konto
authors.initials: YK
authors.lastname: Ghiorghi
authors.forename: Karen I
authors.initials: KI
authors.lastname: Zeller
authors.forename: Chi V
authors.initials: CV
authors.lastname: Dang
authors.forename: P Alexandre
authors.initials: PA
authors.lastname: Kaminski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004926:Escherichia coli / Q000378:metabolism; D005786:Gene Expression Regulation; D016678:Genome; D006860:Hydrogen Bonding; D007700:Kinetics; D007778:Lactobacillus / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000502:physiology*; D010430:Pentosyltransferases / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D010430:Pentosyltransferases; C021888:nucleoside deoxyribosyltransferase; C518894:DNPH1 protein, rat; D009699:N-Glycosyl Hydrolases