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Sirtuins: critical regulators at the crossroads between cancer and aging
Abstract
Sirtuins (SIRTs 1-7), or class III histone deacetylases (HDACs), are protein deacetylases/ADP ribosyltransferases that target a wide range of cellular proteins in the nucleus, cytoplasm, and mitochondria for post-translational modification by acetylation (SIRT1, -2, -3 and -5) or ADP ribosylation (SIRT4 and -6). The orthologs of sirtuins in lower organisms play a critical role in regulating lifespan. As cancer is a disease of aging, we discuss the growing implications of the sirtuins in protecting against cancer development. Sirtuins regulate the cellular responses to stress and ensure that damaged DNA is not propagated and that mutations do not accumulate. SIRT1 also promotes replicative senescence under conditions of chronic stress. By participating in the stress response to genomic insults, sirtuins are thought to protect against cancer, but they are also emerging as direct participants in the growth of some cancers. Here, we review the growing implications of sirtuins both in cancer prevention and as specific and novel cancer therapeutic targets.
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SIRT1 orthologs can deacetylate transcription factors such as p53, NF-kB, and E2F.
“SIRT1 orthologs not only remove acetyl groups from histone tails, they can also deacetylate transcription factors such as p53, NF-kB, and E2F (Haigis and Guarente 2006;Saunders and Verdin 2007;Feige and Auwerx 2008).”
From Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP (2010) · cites this paper as Saunders and Verdin 2007
Citations
Cites
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BackgroundRb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
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Backgroundp53 mutant mice that display early ageing-associated phenotypes
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“Interestingly, transgenic mice expressing a truncated form of p53, which has high activity, are resistant to tumor formation, yet show premature signs of aging and have a shorter lifespan (Tyner et al., 2002).”
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Metadata
- Authors
- Saunders, L. R., & Verdin, E.
- Venue
- Oncogene
- Published
- 2007-08-13
- Volume
- 26
- Issue
- 37
- Pages
- 5489-5504
- ISSN
- 0950-9232
- 1476-5594
- Cited by
- 489
- References
- 17
- Language
- en
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