کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9126870 | 1569961 | 2005 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Targeted disruption of cytosolic SIR2 deacetylase discloses its essential role in Leishmania survival and proliferation
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کلمات کلیدی
ORFHDACLeishmania infantumPFGEnicotinamide-adenine dinucleotide - nikotinamide-adenine dinucleotideGene disruption - اختلال ژنPulse field gel electrophoresis - الکتروفورز ژل فیلد پالسopen reading frame - قاب خواندن بازNAD - نادانhistone deacetylase - هیستون داستیلازVirulence - ویروسی شدنCell cycle - چرخه سلولی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
ژنتیک
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Proteins of the SIR2 family are characterized by a conserved catalytic domain that exerts unique NAD-dependent deacetylase activity on histone and various other cellular substrates. Functional analyses of such proteins have been carried out in a number of prokaryotes and eukaryotes organisms but until now, none have described an essential function for any SIR2 genes. Here using genetic approach, we report that a cytosolic SIR2 homolog in Leishmania is determinant to parasite survival. L. infantum promastigote tolerates deletion of one wild-type LiSIR2 allele (LiSIR2+/â) but achievement of null chromosomal mutants (LiSIR2â/â) requires episomal rescue. Accordingly, plasmid cure shows that these parasites maintain episome even in absence of drug pressure. Though single LiSIR2 gene disruption (LiSIR2+/â) does not affect the growth of parasite in the promastigote form, axenic amastigotes display a marked reduction in their capacity to multiply in vitro inside macrophages and in vivo in Balb/c mice. Taken together these data support a stage specific requirement and/or activity of the Leishmania cytosolic SIR2 protein and reveal an unrelated essential function for the life cycle of this unicellular pathogenic organism. The lack of an effective vaccine against leishmaniasis, and the need for alternative drug treatments, makes LiSIR2 protein a new attractive therapeutic target.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gene - Volume 363, 19 December 2005, Pages 85-96
Journal: Gene - Volume 363, 19 December 2005, Pages 85-96
نویسندگان
Baptiste Vergnes, Denis Sereno, Joana Tavares, Anabela Cordeiro-da-Silva, Laurent Vanhille, Niloufar Madjidian-Sereno, Delphine Depoix, Adriano Monte-Alegre, Ali Ouaissi,