| First Author | Ramsey KM | Year | 2009 |
| Journal | Science | Volume | 324 |
| Issue | 5927 | Pages | 651-4 |
| PubMed ID | 19299583 | Mgi Jnum | J:147991 |
| Mgi Id | MGI:3843127 | Doi | 10.1126/science.1171641 |
| Citation | Ramsey KM, et al. (2009) Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science 324(5927):651-4 |
| abstractText | The circadian clock is encoded by a transcription-translation feedback loop that synchronizes behavior and metabolism with the light-dark cycle. Here we report that both the rate-limiting enzyme in mammalian nicotinamide adenine dinucleotide (NAD+) biosynthesis, nicotinamide phosphoribosyltransferase (NAMPT), and levels of NAD+ display circadian oscillations that are regulated by the core clock machinery in mice. Inhibition of NAMPT promotes oscillation of the clock gene Per2 by releasing CLOCK:BMAL1 from suppression by SIRT1. In turn, the circadian transcription factor CLOCK binds to and up-regulates Nampt, thus completing a feedback loop involving NAMPT/NAD+ and SIRT1/CLOCK:BMAL1. |
