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.
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.
Rongvaux
Anthony
A
Laboratoire de Physiologie Animale, Université Libre de Bruxelles, Gosselies, Belgium.
Shea
Robin J
RJ
Mulks
Martha H
MH
Gigot
Daniel
D
Urbain
Jacques
J
Leo
Oberdan
O
Andris
Fabienne
F
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
D016207:Cytokines; D009243:NAD; D010430:Pentosyltransferases; D054409:Nicotinamide Phosphoribosyltransferase; C495867:nicotinamide phosphoribosyltransferase, mouse