The c-Myc target gene Rcl (C6orf108) encodes a novel enzyme, deoxynucleoside 5'-monophosphate N-glycosidase.
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.
Ghiorghi
Yoan Konto
YK
Unité de Chimie Organique, CNRS Unité de Recherche Associée 2128, Institut Pasteur, 25-28 Rue du Dr. Roux, 75724 Paris Cedex 15, France.
Zeller
Karen I
KI
Dang
Chi V
CV
Kaminski
P Alexandre
PA
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
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