The c-MYC oncoprotein, the NAMPT enzyme, the SIRT1-inhibitor DBC1, and the SIRT1 deacetylase form a positive feedback loop [Medical Sciences]
Silent information regulator 1 (SIRT1) represents an NAD+-dependent deacetylase that inhibits proapoptotic factors including p53. Here we determined whether SIRT1 is downstream of the prototypic c-MYC oncogene, which is activated in the majority of tumors. Elevated expression of c-MYC in human colorectal cancer correlated with increased SIRT1 protein levels. Activation of a conditional c-MYC allele induced increased levels of SIRT1 protein, NAD+, and nicotinamide-phosphoribosyltransferase (NAMPT) mRNA in several cell types. This increase in SIRT1 required the induction of the NAMPT gene by c-MYC. NAMPT is the rate-limiting enzyme of the NAD+ salvage pathway and enhances SIRT1 activity by increasing the amount of NAD+. c-MYC also contributed to SIRT1 activation by sequestering the SIRT1 inh...div id=medwormpbiMedWorm Message:/i/b Please have a look at this new site driven by MedWorm: a href=http://www.thebreastcancerdaily.com/ target=_blankThe Breast Cancer Daily/a/p/div

MINIREVIEW: Redox Sensing and Regulation [Signal Transduction]
Introduction The cache of coupled reduction-oxidation (i.e. redox) reactions in mammals is ultimately enabled by the cellular nicotinamide currency, i.e. the NAD+/NADH and NADP+/NADPH redox couples. Oxidative metabolism, which results in the capture of reducing equivalents primarily as NADH, represents capital investment, whereas biosynthetic reactions, which utilize NADPH, represent expenditures. From the central nicotinamide warehouse, conversion to alternative currencies diversifies the cellular energy portfolio. The mitochondrial membrane is the site of currency conversion to ATP, which occurs via the electron transfer chain and involves a four-electron reduction of oxygen to water. The oxidative phosphorylation process is, however, leaky, and reactive oxygen species (ROS),2 representi...