Journal ArticleDOI
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.
Anthony Rongvaux,Robin J. Shea,Martha H. Mulks,Daniel Gigot,Jacques Urbain,Oberdan Leo,Fabienne Andris +6 more
TLDR
It is demonstrated that 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, and NAD biosynthesis may play an important role in lymphocyte activation.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.read more
Citations
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Journal ArticleDOI
Mammalian sirtuins: biological insights and disease relevance.
TL;DR: There have been major advances in the understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span, and the challenges that will confront the field in the coming years are discussed.
Journal ArticleDOI
NAD+/NADH and NADP+/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences
TL;DR: Future investigation into the metabolism and biological functions of NAD and NADP may expose fundamental properties of life, and suggest new strategies for treating diseases and slowing the aging process.
Journal ArticleDOI
NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus.
TL;DR: This review summarizes how NAD(+) metabolism links energy status with adaptive cellular and organismal responses and how this knowledge can be therapeutically exploited.
Journal ArticleDOI
The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells.
TL;DR: It is found that Nampt was the ratelimiting component in this mammalian NAD biosynthesis pathway and regulates the function of Sir2α and thereby plays an important role in controlling various biological events in mammals.
Journal ArticleDOI
Nutrient-Sensitive Mitochondrial NAD+ Levels Dictate Cell Survival
Hongying Yang,Tianle Yang,Joseph A. Baur,Evelyn Perez,Takashi Matsui,Juan Carmona,Dudley W. Lamming,Nadja C. de Souza-Pinto,Vilhelm A. Bohr,Anthony Rosenzweig,Rafael de Cabo,Anthony A. Sauve,David A. Sinclair +12 more
TL;DR: Rodents fasted for 48 hr show increased levels of the NAD(+) biosynthetic enzyme Nampt and a concomitant increase in mitochondrial NAD(+) and the relevance of these findings to understanding how nutrition modulates physiology and to the evolution of apoptosis is discussed.
References
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