Publications (37) View all
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Article: Adenosine Nucleotide Biosynthesis and AMPK Regulate Adult Life Span and Mediate the Longevity Benefit of Caloric Restriction in Flies.
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ABSTRACT: A common thread among conserved life span regulators lies within intertwined roles in metabolism and energy homeostasis. We show that heterozygous mutations of AMP biosynthetic enzymes extend Drosophila life span. The life span benefit of these mutations depends upon increased AMP:ATP and ADP:ATP ratios and adenosine monophosphate-activated protein kinase (AMPK). Transgenic expression of AMPK in adult fat body or adult muscle, key metabolic tissues, extended life span, while AMPK RNAi reduced life span. Supplementing adenine, a substrate for AMP biosynthesis, to the diet of long-lived AMP biosynthesis mutants reversed life span extension. Remarkably, this simple change in diet also blocked the prolongevity effects of dietary restriction. These data establish AMP biosynthesis, adenosine nucleotide ratios, and AMPK as determinants of adult life span; provide a mechanistic link between cellular anabolism and energy sensing pathways; and indicate that dietary adenine manipulations might alter metabolism to influence animal life span.Cell metabolism 01/2013; 17(1):101-12. · 17.35 Impact Factor -
Article: Correction: Minibrain/Dyrk1a Regulates Food Intake through the Sir2-FOXO-sNPF/NPY Pathway in Drosophila and Mammals.
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ABSTRACT: [This corrects the article on p. e1002857 in vol. 8.].PLoS Genetics 09/2012; 8(9). · 8.69 Impact Factor -
Article: Minibrain/Dyrk1a regulates food intake through the Sir2-FOXO-sNPF/NPY pathway in Drosophila and mammals.
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ABSTRACT: Feeding behavior is one of the most essential activities in animals, which is tightly regulated by neuroendocrine factors. Drosophila melanogaster short neuropeptide F (sNPF) and the mammalian functional homolog neuropeptide Y (NPY) regulate food intake. Understanding the molecular mechanism of sNPF and NPY signaling is critical to elucidate feeding regulation. Here, we found that minibrain (mnb) and the mammalian ortholog Dyrk1a target genes of sNPF and NPY signaling and regulate food intake in Drosophila melanogaster and mice. In Drosophila melanogaster neuronal cells and mouse hypothalamic cells, sNPF and NPY modulated the mnb and Dyrk1a expression through the PKA-CREB pathway. Increased Dyrk1a activated Sirt1 to regulate the deacetylation of FOXO, which potentiated FOXO-induced sNPF/NPY expression and in turn promoted food intake. Conversely, AKT-mediated insulin signaling suppressed FOXO-mediated sNPF/NPY expression, which resulted in decreasing food intake. Furthermore, human Dyrk1a transgenic mice exhibited decreased FOXO acetylation and increased NPY expression in the hypothalamus, as well as increased food intake. Our findings demonstrate that Mnb/Dyrk1a regulates food intake through the evolutionary conserved Sir2-FOXO-sNPF/NPY pathway in Drosophila melanogaster and mammals.PLoS Genetics 08/2012; 8(8):e1002857. · 8.69 Impact Factor -
Article: JNK/FOXO mediated PeroxiredoxinV expression regulates redox homeostasis during Drosophila melanogaster gut infection.
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ABSTRACT: Innate immunity plays an important role in combating microbial infection in animals. During bacterial infection in Drosophila melanogaster gut, Dual oxidase (Duox) generates reactive oxygen species (ROS) to fight against the infected microbes. Concurrently, antioxidant systems eliminate residual ROS and protect the hosts. Here we found that Drosophila melanogaster Peroxiredoxin V (dPrxV) is an immune-related antioxidant enzyme which maintains intestinal redox homeostasis. dPrxV was highly expressed in gut and induced by the oral infection of Erwinia carotovora carotovora. dPrxV expression was increased by the gut-specific Duox overexpression but decreased by Duox inhibition. Moreover, dPrxV expression was mediated by the JNK/FOXO signaling and dPrxV mutant reduced survival after gut infection. These results suggest that JNK/FOXO mediated dPrxV expression plays a critical role in Drosophila melanogaster gut during bacterial infection in protecting the host gut epithelial cells from oxidative damage.Developmental and comparative immunology 07/2012; · 3.29 Impact Factor -
Article: Inhibition of p53 acetylation by INHAT subunit SET/TAF-Iβ represses p53 activity.
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ABSTRACT: The tumor suppressor p53 responds to a wide variety of cellular stress signals. Among potential regulatory pathways, post-translational modifications such as acetylation by CBP/p300 and PCAF have been suggested for modulation of p53 activity. However, exactly how p53 acetylation is modulated remains poorly understood. Here, we found that SET/TAF-Iβ inhibited p300- and PCAF-mediated p53 acetylation in an INHAT (inhibitor of histone acetyltransferase) domain-dependent manner. SET/TAF-Iβ interacted with p53 and repressed transcription of p53 target genes. Consequently, SET/TAF-Iβ blocked both p53-mediated cell cycle arrest and apoptosis in response to cellular stress. Using different apoptosis analyses, including FACS, TUNEL and BrdU incorporation assays, we also found that SET/TAF-Iβ induced cellular proliferation via inhibition of p53 acetylation. Furthermore, we observed that apoptotic Drosophila eye phenotype induced by either dp53 overexpression or UV irradiation was rescued by expression of dSet. Inhibition of dp53 acetylation by dSet was observed in both cases. Our findings provide new insights into the regulation of stress-induced p53 activation by HAT-inhibiting histone chaperone SET/TAF-Iβ.Nucleic Acids Research 09/2011; 40(1):75-87. · 8.03 Impact Factor
