Identification of a class of small molecule inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening.
Christina M. Grozinger,Elizabeth D. Chao,Helen E. Blackwell,Danesh Moazed,Stuart L. Schreiber +4 more
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TLDR
A high throughput, phenotypic screen in cells that led to the discovery of a class of sirtuin inhibitors, and structure-activity relationship analysis of the compounds identified a key hydroxy-napthaldehyde moiety that is necessary and sufficient for inhibitory activity.About:
This article is published in Journal of Biological Chemistry.The article was published on 2001-10-19 and is currently open access. It has received 548 citations till now. The article focuses on the topics: Sirtuin & Deacetylase activity.read more
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The Sir2 Family of Protein Deacetylases
Gil Blander,Leonard Guarente +1 more
TL;DR: The role of NAD+, the unusual products of the deacetylation reaction, the Sir2 structure, and the Sir1 and Sir2 chemical inhibitors and activators that were recently identified are discussed.
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The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase
TL;DR: A human ortholog of Sir2p, sirtuin type 2 (SIRT2), is a predominantly cytoplasmic protein that colocalizes with microtubules and is established as a bona fide tubulin deacetylase.
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SIRT1 Regulates Circadian Clock Gene Expression through PER2 Deacetylation
Gad Asher,David Gatfield,Markus Stratmann,Hans Reinke,Charna Dibner,Florian Kreppel,Raul Mostoslavsky,Frederick W. Alt,Ueli Schibler +8 more
TL;DR: It is shown that SIRT1, an NAD(+)-dependent protein deacetylase, is required for high-magnitude circadian transcription of several core clock genes, including Bmal1, Rorgamma, Per2, and Cry1.
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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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Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration.
TL;DR: It is demonstrated that increased Nmnat activity is responsible for the axon-sparing activity of the Wlds protein and that SIRT1, a mammalian ortholog of Sir2, is the downstream effector of increased NMNat activity that leads to axonal protection.
References
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A revised medium for rapid growth and bio assays with tobacco tissue cultures
Toshio Murashige,Folke Skoog +1 more
TL;DR: In vivo redox biosensing resolves the spatiotemporal dynamics of compartmental responses to local ROS generation and provide a basis for understanding how compartment-specific redox dynamics may operate in retrograde signaling and stress 67 acclimation in plants.
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Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
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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Target-oriented and diversity-oriented organic synthesis in drug discovery.
TL;DR: Several synthetic planning principles for diversity-oriented synthesis and their role in the drug discovery process are presented in this review.
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Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
TL;DR: In this paper, the lifespan of C. elegans strains containing duplications of chromosomal regions was surveyed and it was shown that a duplication containing sir-2.1-the SIR2 gene most homologous to yeast-confers a lifespan that is extended by up to 50%.
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Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae
TL;DR: These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD, the oxidized form of nicotinamide adenine dinucleotide.