title: Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis.
abstract: The murine homologue of the previously identified human "pre-B-cell colony-enhancing factor" (PBEF) gene coding for a putative cytokine has been identified by screening a subtractive library enriched in genes expressed in activated T lymphocytes. Unlike most cytokine genes known to date, the PBEF gene is ubiquitously expressed in lymphoid and non-lymphoid tissues and displays significant homology with genes from primitive metazoans (marine sponges) and prokaryotic organisms. Recently, a bacterial protein encoded by nadV, a gene from the prokaryote Haemophilus ducreyi displaying significant homology with PBEF, has been identified as a nicotinamide phosphoribosyltranferase (NAmPRTase), an enzyme involved in nicotinamide adenine dinucleotide (NAD) biosynthesis. Using a panel of antibodies to murine PBEF, we demonstrate in this work that, similarly to its microbial counterpart, the murine protein is a NAmPRTase, catalyzing the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. The role of PBEF as a NAmPRTase was further confirmed by showing that the mouse gene was able to confer the ability to grow in the absence of NAD to a NAmPRTase-defective bacterial strain. The present findings are in keeping with the ubiquitous nature of this protein, and indicate that NAD biosynthesis may play an important role in lymphocyte activation.
authors.affiliation: Laboratoire de Physiologie Animale, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rongvaux
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shea
authors.forename: Martha H
authors.initials: MH
authors.lastname: Mulks
authors.forename: Daniel
authors.initials: D
authors.lastname: Gigot
authors.forename: Jacques
authors.initials: J
authors.lastname: Urbain
authors.forename: Oberdan
authors.initials: O
authors.lastname: Leo
authors.forename: Fabienne
authors.initials: F
authors.lastname: Andris
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016207:Cytokines / Q000737:chemistry / Q000502:physiology*; D003600:Cytosol / Q000201:enzymology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009243:NAD / Q000096:biosynthesis*; D054409:Nicotinamide Phosphoribosyltransferase; D010430:Pentosyltransferases / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D009243:NAD; D010430:Pentosyltransferases; D054409:Nicotinamide Phosphoribosyltransferase; C495867:nicotinamide phosphoribosyltransferase, mouse