Biological and Potential Therapeutic Roles of Sirtuin Deacetylases

Taylor, David; Maxwell, Michele M.; Lüthi-Carter, Ruth; Kazantsev, Aleksey G.

doi:10.1007/s00018-008-8357-y

Cited by 123 publications

(129 citation statements)

References 195 publications

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“…They regulate a variety of cellular functions, such as genome maintenance, longevity, and metabolism (Oberdoerffer and Sinclair, 2007;Westphal et al, 2007;Yamamoto et al, 2007). Until now, all sirtuins, except for SIRT4, have been described to have deacetylation (Taylor et al, 2008). The SIRT proteins exhibit differential localization from nucleus to nucleolus, and from cytoplasm to mitochondria (Sauve et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

SIRT2 regulates NF-κB-dependent gene expression through deacetylation of p65 Lys310

Rothgiesser

Erener

Waibel

et al. 2010

Journal of Cell Science

330

254

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SummaryNF-kB regulates the expression of a large number of target genes involved in the immune and inflammatory response, apoptosis, cell proliferation, differentiation and survival. In this study, we identified SIRT2 as a deacetylase of the transcription factor p65. SIRT2 is a member of the family of sirtuins, which are NAD + -dependent deacetylases involved in several cellular processes. SIRT2 interacts with p65 in the cytoplasm and deacetylates p65 in vitro and in vivo at Lys310. Moreover, p65 is hyperacetylated at Lys310 in Sirt2 -/-cells after TNFa stimulation, which results in the increase in expression of a subset of p65 acetylation-dependent target genes. Our work provides evidence that p65 is deacetylated by SIRT2 in the cytoplasm to regulate the expression of specific NF-kBdependent genes.

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Section: Introductionmentioning

confidence: 99%

SIRT2 regulates NF-κB-dependent gene expression through deacetylation of p65 Lys310

Rothgiesser

Erener

Waibel

et al. 2010

Journal of Cell Science

330

254

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“…34 Together with IGF-1 and mTOR, sirtuins mediate the longevity effects of the dietary regime known as caloric restriction. 36,37 Recent findings demonstrate that the activity of sirtuins is also implicated in cancer progression, affecting the activity of p53, 38,39 as well as that of other regulators.…”

Section: The Role Of Dna Damage In Aging and Cancermentioning

confidence: 99%

Aging and Cancer: Converging Routes to Disease Prevention

Chobotova

2009

Integr Cancer Ther

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A ging is often associated with neurological and physical deterioration and the development of diseases, including Parkinson's, Alzheimer's, diabetes, cardiovascular diseases, and cancer. Cancer is one of the diseases that drastically diminish quality of life and life expectancy. Extensive research into the molecular mechanisms of both aging and cancer has demonstrated the interrelatedness of their biological pathways.The most important of these pathways are the ones activated by DNA damage, depletion of stem cells, oxidative stress, and psychological stress. These pathways initiate multiple cascades of molecular signals that crossreact with each other, thereby activating the regulators of aging and cancer. Of these, the most interesting are the regulators of metabolism that respond directly to nutrient and energy cues. It is now becoming possible to infer from this evidence that external factors have a direct role in regulating aging and cancer. These include diet, physical activity, and stress control. This article will assess recent evidence linking the mechanisms of aging and cancer as well as surveying research on the effectiveness of natural approaches affecting these mechanisms. Aging and Cancer: Converging Routes to Disease PreventionKatya Chobotova, DPhilAn integrative approach to the combined challenges of aging, cancer and stress is a necessary part of a global vision of wellness. Recent research into the mechanisms of aging, cancer and stress has established the biological links between these processes. Understanding these links is an important stepping-stone for developing approaches and therapies that ensure wellness throughout all stages of aging. This paper will consider the most recent developments in research into the molecular mechanisms common to aging and cancer and will discuss the effectiveness of natural approaches for preventing disease. Metabolic regulators as well as nutrient and energy sensors are involved in the processes of aging and cancer, and these are open to external manipulation and control. It is now becoming possible to demonstrate how nutrition, physical activity and stress control can lead to disease-free aging.

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“…However, it was later found that these enzymes act as sensors of the cellular energy status, establishing a link between gene silencing and metabolism in vivo (Denu, 2003). Therefore, in the past decade, research was aimed at elucidating their structure (Sanders et al, 2010), enzymatic activity (Taylor et al, 2008), biology and function in the cell (Shoba et al, 2009), target proteins that include -besides histonestranscription factors that regulate stress, metabolism and survival pathways (Shoba et al, 2009), as well as natural and synthetic compounds that activate (Howitz et al, 2003;Camins et al, 2010) and inhibit (Cen, 2010;Lawson et al, 2010) them. Further general information on sirtuins is available in the reviews by Dali-Youcef et al (2007), Shoba et al (2009), Imai andGuarente (2010), Rajendran et al (2011) andCantó andAuwerx (2012); information on the controversy arising about the role of sirtuins in lifespan regulation can be found in the work by Burnett et al (2011); information on resveratrol, the principal sirtuin activator being studied and its role in mammalian biology can be found in the review by Pervaiz (2003).…”

Section: Introductionmentioning

confidence: 99%

Potential role of sirtuins in livestock production

Ghinis-Hozumi

Antaramián

Villarroya

et al. 2013

Animal

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Sirtuins are NAD+-dependent histone and protein deacetylases, which have been studied during the last decade with a focus on their role in lifespan extension and age-related diseases under normal and calorie-restricted or pathological conditions. However, sirtuins also have the ability to regulate energy homeostasis as they can sense the metabolic state of the cell through the NAD+/NADH ratio; hence, changes in the diet can modify the expression of these enzymes. Dietary manipulations are a common practice currently being used in livestock production with favorable results, probably due in part to the enhanced activity of sirtuins. Nevertheless, sirtuin expression in livestock species has not been a research target. For these reasons, the goal of this review is to awaken interest in these enzymes for future detailed characterization in livestock species by presenting a general introduction to what sirtuins are, how they work and what is known about their role in livestock.

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Biological and Potential Therapeutic Roles of Sirtuin Deacetylases

Cited by 123 publications

References 195 publications

SIRT2 regulates NF-κB-dependent gene expression through deacetylation of p65 Lys310

SIRT2 regulates NF-κB-dependent gene expression through deacetylation of p65 Lys310

Aging and Cancer: Converging Routes to Disease Prevention

Potential role of sirtuins in livestock production

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