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Article
The glutathione S-transferase Gstt1 drives survival and dissemination in metastases
Identifying the adaptive mechanisms of metastatic cancer cells remains an elusive question in the treatment of metastatic disease, particularly in pancreatic cancer (pancreatic adenocarcinoma, PDA). A loss-of-...
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Article
Inhibition of the proline metabolism rate-limiting enzyme P5CS allows proliferation of glutamine-restricted cancer cells
Glutamine is a critical metabolite for rapidly proliferating cells as it is used for the synthesis of key metabolites necessary for cell growth and proliferation. Glutamine metabolism has been proposed as a th...
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Article
Open AccessSIRT6 is a key regulator of mitochondrial function in the brain
The SIRT6 deacetylase has been implicated in DNA repair, telomere maintenance, glucose and lipid metabolism and, importantly, it has critical roles in the brain ranging from its development to neurodegeneratio...
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Article
Open AccessSirtuin 6 inhibition protects against glucocorticoid-induced skeletal muscle atrophy by regulating IGF/PI3K/AKT signaling
Chronic activation of stress hormones such as glucocorticoids leads to skeletal muscle wasting in mammals. However, the molecular events that mediate glucocorticoid-induced muscle wasting are not well understo...
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Article
Open AccessA non-dividing cell population with high pyruvate dehydrogenase kinase activity regulates metabolic heterogeneity and tumorigenesis in the intestine
Although reprogramming of cellular metabolism is a hallmark of cancer, little is known about how metabolic reprogramming contributes to early stages of transformation. Here, we show that the histone deacetylas...
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Article
TiPpIng the balance in histone acetylation
Nutrient availability and the cell cycle are known to affect chromatin accessibility. A fundamental question is which mechanisms are involved in connecting nutrient levels, the cell cycle and chromatin regulat...
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Article
A unique subset of glycolytic tumour-propagating cells drives squamous cell carcinoma
Head and neck squamous cell carcinoma (SCC) remains among the most aggressive human cancers. Tumour progression and aggressiveness in SCC are largely driven by tumour-propagating cells (TPCs). Aerobic glycolys...
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Article
Nuclear metabolism and the regulation of the epigenome
Cellular metabolism has emerged as a major biological node governing cellular behaviour. Metabolic pathways fuel cellular energy needs, providing basic chemical molecules to sustain cellular homeostasis, proli...
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Article
Open AccessSIRT6-dependent cysteine monoubiquitination in the PRE-SET domain of Suv39h1 regulates the NF-κB pathway
Sirtuins are NAD+-dependent deacetylases that facilitate cellular stress response. They include SirT6, which protects genome stability and regulates metabolic homeostasis through gene silencing, and whose loss in...
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Chapter and Conference Paper
Role of Sirtuins in Retinal Function Under Basal Conditions
Sirtuins are NAD+-dependent enzymes that govern cellular homeostasis by regulating the acylation status of their diverse target proteins. We recently demonstrated that both rod and cone photoreceptors rely on NAM...
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Article
SIRT6: a new guardian of mitosis
The sirtuin family protein SIRT6 is a stress-responsive NAD-dependent histone deacetylase with key roles in glucose homeostasis, DNA repair and cellular lifespan. SIRT6 is now shown to mediate deacetylation of...
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Article
High mobility group protein-mediated transcription requires DNA damage marker γ-H2AX
The eukaryotic genome is organized into chromatins, the physiological template for DNA-dependent processes including replication, recombination, repair, and transcription. Chromatin-mediated transcription regu...
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Article
The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine
How embryonic stem cells (ESCs) commit to specific cell lineages and yield all cell types of a fully formed organism remains a major question. ESC differentiation is accompanied by large-scale histone and DNA ...
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Article
Metabolism, longevity and epigenetics
Metabolic homeostasis and interventions that influence nutrient uptake are well-established means to influence lifespan even in higher eukaryotes. Until recently, the molecular mechanisms explaining such an ef...
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Article
SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine
The sirtuin family of enzymes are known as NAD-dependent deacetylases, although some of them have very weak deacetylase activity; here human SIRT6, an enzyme important for DNA repair and transcription, is show...
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Protocol
Assaying Chromatin Sirtuins
Most of the sirtuins’ nuclear substrates identified so far are histones or other chromatin-associated proteins and, thus, it is of special relevance the development of good biochemical techniques to analyze th...
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Article
The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun
The chromatin-modifying protein SIRT6 has previously been shown to have anti-aging properties. Sundaresan et al. now show that SIRT6 expression is low in failing human hearts and SIRT6 in mice protects the heart ...
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Article
Open AccessThe histone deacetylase SIRT6, a critical modulator of metabolism and tumorigenesis
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Article
Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase
Notch signalling coordinates angiogenesis by controlling the specification of endothelial cells into tip cells that lead the way in growing blood vessels and the stalk cells that follow. Michael Potente and co...
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Chapter
Characterization of Nuclear Sirtuins: Molecular Mechanisms and Physiological Relevance
Sirtuins are protein deacetylases/mono-ADP-ribosyltransferases found in organisms ranging from bacteria to humans. This group of enzymes relies on nicotinamide adenine dinucleotide (NAD+) as a cofactor linking th...
