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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Gene Review: 

SIRT4  -  sirtuin 4

Homo sapiens

Synonyms: NAD-dependent ADP-ribosyltransferase sirtuin-4, NAD-dependent protein deacetylase sirtuin-4, Regulatory protein SIR2 homolog 4, SIR2-like protein 4, SIR2L4
 
 
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Disease relevance of SIRT4

  • Loss of SIRT4 in insulinoma cells activates GDH, thereby upregulating amino acid-stimulated insulin secretion [1].
 

High impact information on SIRT4

  • SIRT4 Inhibits Glutamate Dehydrogenase and Opposes the Effects of Calorie Restriction in Pancreatic beta Cells [1].
  • These results indicate that SIRT4 functions in beta cell mitochondria to repress the activity of GDH by ADP-ribosylation, thereby downregulating insulin secretion in response to amino acids, effects that are alleviated during CR [1].
  • Furthermore, GDH from SIRT4-deficient or CR mice is insensitive to phosphodiesterase, an enzyme that cleaves ADP-ribose, suggesting the absence of ADP-ribosylation [1].
  • HDAC5 and SIRT4 were consistently underexpressed [2].
  • The SIRT4 and SIRT5 sirtuins more closely resemble prokaryotic sirtuin sequences [3].
 

Associations of SIRT4 with chemical compounds

References

  1. SIRT4 Inhibits Glutamate Dehydrogenase and Opposes the Effects of Calorie Restriction in Pancreatic beta Cells. Haigis, M.C., Mostoslavsky, R., Haigis, K.M., Fahie, K., Christodoulou, D.C., Murphy, A.J., Valenzuela, D.M., Yancopoulos, G.D., Karow, M., Blander, G., Wolberger, C., Prolla, T.A., Weindruch, R., Alt, F.W., Guarente, L. Cell (2006) [Pubmed]
  2. Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors. Bradbury, C.A., Khanim, F.L., Hayden, R., Bunce, C.M., White, D.A., Drayson, M.T., Craddock, C., Turner, B.M. Leukemia (2005) [Pubmed]
  3. Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Frye, R.A. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  4. Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase. Ahuja, N., Schwer, B., Carobbio, S., Waltregny, D., North, B.J., Castronovo, V., Maechler, P., Verdin, E. J. Biol. Chem. (2007) [Pubmed]
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