Home

About

Advanced Search

Browse by Discipline

Scientific Societies

E-print Alerts

Add E-prints

E-print Network
FAQHELPSITE MAPCONTACT US


  Advanced Search  

 
Intracellular NAD levels regulate tumor necrosis factor protein synthesis in a sirtuin-dependent manner
 

Summary: Intracellular NAD levels regulate tumor necrosis factor
protein synthesis in a sirtuin-dependent manner
Fre´de´ric Van Gool1,8, Mara Galli´1,8, Cyril Gueydan2, Ve´ronique Kruys2, Pierre-Paul Prevot3,7,
Antonio Bedalov4, Raul Mostoslavsky5,7, Frederick W Alt5, Thibaut De Smedt6,7 & Oberdan Leo1
Tumor necrosis factor (TNF) synthesis is known to play a
major part in numerous inflammatory disorders, and multiple
transcriptional and post-transcriptional regulatory mechanisms
have therefore evolved to dampen the production of this
key proinflammatory cytokine1,2. The high expression of
nicotinamide phosphoribosyltransferase (Nampt), an enzyme
involved in the nicotinamide-dependent NAD biosynthetic
pathway, in cells of the immune system3 has led us to
examine the potential relationship between NAD metabolism
and inflammation. We show here that intracellular NAD
concentration promotes TNF synthesis by activated immune
cells. Using a positive screen, we have identified Sirt6,
a member of the sirtuin family4, as the NAD-dependent
enzyme able to regulate TNF production by acting at a
post-transcriptional step. These studies reveal a previously
undescribed relationship between metabolism and the

  

Source: Alt,, Frederick - Immune Disease Institute, Harvard University

 

Collections: Biology and Medicine