Sirtuin Substrates

Sirtuins are involved in metabolic regulation and play a role in cellular processes like transcription, apoptosis, and inflammation but also diseases like neurodegeneration, diabetes, cardiovascular diseases and cancer. Sirtuins are NAD+ dependent enzymes that possess mono-ADP-ribosyltransferase or deacylase activity. 
SIR2 was first discovered in yeast (silent mating-type information regulation 2) and is highly conserved throughout evolution. Mammals possess seven different sirtuins (SIRT1–7) that are active in various cellular organelles e.g. nucleus or mitochondria:
  • Sirtuin 1 (SIRT1) has been shown to represses p53-mediated tumor suppression and may display tumor-suppressive or oncogenic roles, depending on the type and stage of cancer.
  • Sirtuin 3 (SIRT3) plays a role in the regulation of glycolysis and angiogenesis genes, which can increase tumor growth.
  • Sirtuin 4 (SIRT4) regulates glutamine metabolism. The loss of SIRT4 in tumor cells leads to enhanced glutamine catabolism promoting tumor growth.
  • Sirtuin 6 (SIRT6) regulates cancer metabolism and inflammation. Loss of SIRT6 results in increased glycolysis and glutaminolysis, which favor tumorigenesis.
  • Additionally, SIRT1 and SIRT6 regulate DNA break-repair pathways.

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