Return of SIRT1 deacetylase – Why is SIRT1 so attractive in Drug discovery and Stem cell research?

Primary cells, active enzymes and small molecules for stem cell and Drug discovery research
SIRT1 is a NAD dependent class III Histone Deacetylase (HDAC). The tumor suppressor p53 is not the unique SIRT1 substrate. SIRT1 also deacetylates various key protein targets (PTEN, FOX, HIF-1, XPA, SMAD7 …) involved in the regulation of cellular survival, proliferation and angiogenesis.

SIRT1 – an attractive druggable target in oncologyPrimary cells, active enzymes and small molecules for stem cell and Drug discovery research

SIRT1 has rapidly been considered a valuable druggable target because of its implication in p53-dependent apoptosis in response to cellular stress and DNA damage. This enthusiasm was even more enhanced in 2011 when certain studies suggested that a natural dietary polyphenolic compound (Resveratrol) could promote healthy ageing and increase mouse and yeast life span through activation of sirtuins. (1)
Today, SIRT1 returns to the front of the stage with its possible involvement in cellular reprogramming and pluripotency.

SIRT1 – an attractive candidate in regenerative medicine

De Bonis at al. have recently shown the role of SIRT1 as a modulator of cell pluripotency and differentiation. (2)
The authors showed that SIRT1, by interacting with c-myc, is necessary for telomere elongation, and influences telomeric structure and transcription after cell reprogramming. They confirmed that SIRT1 is required for genomic stability of iPSCs and is involved in the maintenance of “good-quality” iPSCs.
Due to its role in chromatin remodeling, gene expression regulation and genomic stability, SIRT1 is again a source of inspiration for researchers in drug discovery, cancer research and cellular reprogramming.
(1) Fernández al. “The effects of the dietary polyphenol resveratrol on human healthy aging and lifespan” (2011) Epigenetics, Vol. 6 Issue 7, 870-8. DOI: 10.4161/epi.6.7.16499.
(2) De Bonis M.L. et al. “SIRT1 Is Necessary for Proficient Telomere Elongation and Genomic Stability of Induced Pluripotent Stem Cells” (2014) Stem Cell Reports, Vol. 2, 1–17. DOI: 10.1016/j.stemcr.2014.03.002

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