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Open AccessJournal ArticleDOI

Sirtuins: critical regulators at the crossroads between cancer and aging.

Laura Saunders, +1 more
- 13 Aug 2007 - 
- Vol. 26, Iss: 37, pp 5489-5504
TLDR
The growing implications of sirtuins both in cancer prevention and as specific and novel cancer therapeutic targets are reviewed.
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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Citations
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Retrospective study: The diagnostic accuracy of conventional forceps biopsy of gastric epithelial compared to endoscopic submucosal dissection (STROBE compliant).

TL;DR: According to the analysis, old men plus gastric fundus or antrum of CFB were strongly suggested to perform ESD if precancerous lesions were found and young women with low-grade intraepithelial neoplasia could select regular follow-up.
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The NAD+-Dependent Deacetylase SIRT1 Modulates CLOCK-Mediated Chromatin Remodeling and Circadian Control

TL;DR: It is proposed that SIRT1 functions as an enzymatic rheostat of circadian function, transducing signals originated by cellular metabolites to the circadian clock.
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Cancer epigenetics reaches mainstream oncology

TL;DR: The discovery of mutations in the epigenetic machinery and the approval of the first epigenetic drugs for the treatment of subtypes of leukemias and lymphomas has been an eye-opener for many biomedical scientists and clinicians.
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HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention

TL;DR: 19 articles review various aspects of the enzymes governing lysine acetylation, especially about their intimate links to cancer, and highlight four central themes: multisubunit enzymatic complexes; non-histone substrates in diverse cellular processes; interplay of lysines acetylations with other regulatory mechanisms; and novel therapeutic strategies and preventive measures to combat cancer and other human diseases.
References
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Journal ArticleDOI

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TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
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Journal ArticleDOI

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Journal ArticleDOI

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Journal ArticleDOI

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TL;DR: The analysis of two SIR2 mutations supports the idea that this deacetylase activity accounts for silencing, recombination suppression and extension of life span in vivo, and provides a molecular framework of NAD-dependent histone de acetylation that connects metabolism, genomic silencing and ageing in yeast and, perhaps, in higher eukaryotes.
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