Michael W McBurney

..Thus, SirT1 is an important regulator of energy metabolism and, like its orthologues from simpler eukaryotes, the SirT1 protein appears to be required for a normal response to caloric restriction...

..We interpret these observations as consistent with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease...

..Our results failed to provide evidence that the mammalian SIR2alpha protein plays a role in gene silencing and suggest that the physiological substrate(s) for the SIR2alpha deacetylase may be nuclear proteins other than histones...

..The phenotype of the sir2alpha null animals suggests that the SIR2alpha protein is essential for normal embryogenesis and for normal reproduction in both sexes...

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..However, we show that mice lacking at least one allele of both Sirt1 and Igfbp1 genes have a much higher incidence of malocclusion...

..Thus, the SirT1 protein has functions that can be attributed to the catalytic activity of the protein, as well as other functions that are conferred by the protein itself...

..Thus, the effect of the co-transfected Pgk-1 gene is to inhibit the process of gene inactivation possibly by functioning like an insulator or boundary element in the chromatin...

..These findings suggest that SirT1 does not affect many p53-mediated biological activities despite the fact that acetylated p53 has been shown to be a substrate for SirT1...

..Constitutive expression of Hox 1.6 from a heterologous promoter did not induce differentiation indicating that expression of this gene is insufficient to initiate the cascade of events that culminates in cell differentiation...

..The enhanced integration and expression of transfected plasmids required active transcription through an intragenic region of Pgk-1, perhaps resulting in more recombinogenic plasmid DNAs...

..Loss of control over apoptotic signalling is now recognized as a critical event in the development of cancer. Our results indicate that XAF1 may be important in mediating the apoptosis resistance of cancer cells...

..The promoter of the mouse pgk-1 gene is homologous to the human pgk-1 promoter. A number of conserved motifs in the promoter may indicate a significant role for these sequences in expression of the pgk-1 gene...

..Splicing assays show that CHD1 overexpression can affect alternative splicing. These results suggest that CHD1 may function in both chromatin mediated transcriptional repression and RNA splicing...

..Our evidence suggests that E2F-1 reduces expression from RA-inducible promoters by interacting with an unidentified coactivator(s) that is required by the RARs...

..The pgk-2 gene may, then, be a transcribed retroposon. Thus, gene duplication by retroposition may have been used as a mechanism for evolutionary diversification...

..Thus, our results suggest that SirT1 does not behave like a classical tumor-suppressor gene but the antitumor activity of resveratrol is mediated at least in part by SirT1...

..Our evidence suggests that pgk-1-derived retroposons arose initially more than 100 million years ago and have continued to arise until so recently that some are unique to different mouse strains...

..Thus, the Pgk-1 promoter drives transgene expression in all tissues but the levels of expression are not uniform in each cell...

..A number of other DNA sequence polymorphisms exist between Pgk-1b and Pgk-1a including part of an L1 repeated element unique to Pgk-1a...

..Aggregated D3 cells express Brachyury mRNA suggesting that the mutation(s) responsible for the phenotype of D3 cells is downstream of the chain of events initiated by Brachyury expression...

..Taken together, these results suggest that the interaction between Sirt1 and TLE1 is important for mediating repression of NF-kappaB activity...

..Our findings establish a functional link between the two NAD+-dependent enzyme systems and provide a physiological interpretation for the mechanism of death in cells lacking SIRT1...

..These experiments reveal that AMPK, Nampt, and SIRT1 are the molecular components of a functional signaling pathway that allows skeletal muscle cells to sense and react to nutrient availability...

..These results support a model in which cycles of Tat acetylation and deacetylation regulate HIV transcription. SIRT1 recycles Tat to its unacetylated form and acts as a transcriptional coactivator during Tat transactivation...

..These results are consistent with findings in S. cerevisiae and other model systems, suggesting that mammalian sirtuins can play both protective and proaging roles...

..Furthermore, we provide evidence that such Nmnat1/NAD-mediated protection is primarily mediated by their effects on local bioenergetics. Together, our results suggest a novel molecular pathway for axon degeneration...

..As a reduction in fat is sufficient to extend murine lifespan, our results provide a possible molecular pathway connecting calorie restriction to life extension in mammals...

..These events likely contribute to the state of immune cell hyperactivation found in HIV-infected individuals...