Expression of de novo Pyrimidine Biosynthesis Genes during Spermatogenesis in Drosophila melanogaster

1995 ◽  
pp. 567-574
Author(s):  
Lawrence Porter ◽  
Jun Yang ◽  
John Rawls
Keyword(s):  
Drosophila Melanogaster ◽  
De Novo ◽  
Pyrimidine Biosynthesis

scholarly journals Drosophila Ana2 is a conserved centriole duplication factor

2010 ◽  
Vol 188 (3) ◽  
pp. 313-323 ◽  
Author(s):  
Naomi R. Stevens ◽  
Jeroen Dobbelaere ◽  
Kathrin Brunk ◽  
Anna Franz ◽  
Jordan W. Raff
Keyword(s):  
Drosophila Melanogaster ◽  
Caenorhabditis Elegans ◽  
De Novo ◽  
Protein Family ◽  
Centriole Duplication

In Caenorhabditis elegans, five proteins are required for centriole duplication: SPD-2, ZYG-1, SAS-5, SAS-6, and SAS-4. Functional orthologues of all but SAS-5 have been found in other species. In Drosophila melanogaster and humans, Sak/Plk4, DSas-6/hSas-6, and DSas-4/CPAP—orthologues of ZYG-1, SAS-6, and SAS-4, respectively—are required for centriole duplication. Strikingly, all three fly proteins can induce the de novo formation of centriole-like structures when overexpressed in unfertilized eggs. Here, we find that of eight candidate duplication factors identified in cultured fly cells, only two, Ana2 and Asterless (Asl), share this ability. Asl is now known to be essential for centriole duplication in flies, but no equivalent protein has been found in worms. We show that Ana2 is the likely functional orthologue of SAS-5 and that it is also related to the vertebrate STIL/SIL protein family that has been linked to microcephaly in humans. We propose that members of the SAS-5/Ana2/STIL family of proteins are key conserved components of the centriole duplication machinery.

scholarly journals Original Chemical Series of Pyrimidine Biosynthesis Inhibitors That Boost the Antiviral Interferon Response

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Marianne Lucas-Hourani ◽  
Daniel Dauzonne ◽  
Hélène Munier-Lehmann ◽  
Samira Khiar ◽  
Sébastien Nisole ◽  
...  
Keyword(s):  
Metabolic Pathway ◽  
Defense Mechanisms ◽  
De Novo ◽  
Pyrimidine Biosynthesis ◽  
Interferon Response ◽  
Type I ◽  
Innate Defense ◽  
New Class ◽  
Biosynthesis Inhibitors ◽  
Tightly Coupled

ABSTRACT De novo pyrimidine biosynthesis is a key metabolic pathway involved in multiple biosynthetic processes. Here, we identified an original series of 3-(1H-indol-3-yl)-2,3-dihydro-4H-furo[3,2-c]chromen-4-one derivatives as a new class of pyrimidine biosynthesis inhibitors formed by two edge-fused polycyclic moieties. We show that identified compounds exhibit broad-spectrum antiviral activity and immunostimulatory properties, in line with recent reports linking de novo pyrimidine biosynthesis with innate defense mechanisms against viruses. Most importantly, we establish that pyrimidine deprivation can amplify the production of both type I and type III interferons by cells stimulated with retinoic acid-inducible gene 1 (RIG-I) ligands. Altogether, our results further expand the current panel of pyrimidine biosynthesis inhibitors and illustrate how the production of antiviral interferons is tightly coupled to this metabolic pathway. Functional and structural similarities between this new chemical series and dicoumarol, which was reported before to inhibit pyrimidine biosynthesis at the dihydroorotate dehydrogenase (DHODH) step, are discussed.

scholarly journals Novel AR-12 derivatives, P12-23 and P12-34, inhibit flavivirus replication by blocking host de novo pyrimidine biosynthesis

2018 ◽  
Vol 7 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Chao-Fu Yang ◽  
Balraj Gopula ◽  
Jian-Jong Liang ◽  
Jin-Kun Li ◽  
Si-Yu Chen ◽  
...  
Keyword(s):  
De Novo ◽  
Pyrimidine Biosynthesis

scholarly journals MCT4 regulates de novo pyrimidine biosynthesis in GBM in a lactate-independent manner

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Raffaella Spina ◽  
Dillon M Voss ◽  
Xiaohua Yang ◽  
Jason W Sohn ◽  
Robert Vinkler ◽  
...  
Keyword(s):  
De Novo ◽  
Apoptotic Cell ◽  
Pyrimidine Biosynthesis ◽  
Monocarboxylate Transporter ◽  
Independent Manner ◽  
Pyrimidine Nucleosides ◽  
Significant Prolongation ◽  
Orthotopic Xenografts

Abstract Background Necrotic foci with surrounding hypoxic cellular pseudopalisades and microvascular hyperplasia are histological features found in glioblastoma (GBM). We have previously shown that monocarboxylate transporter 4 (MCT4) is highly expressed in necrotic/hypoxic regions in GBM and that increased levels of MCT4 are associated with worse clinical outcomes. Methods A combined transcriptomics and metabolomics analysis was performed to study the effects of MCT4 depletion in hypoxic GBM neurospheres. Stable and inducible MCT4-depletion systems were used to evaluate the effects of and underlining mechanisms associated with MCT4 depletion in vitro and in vivo, alone and in combination with radiation. Results This study establishes that conditional depletion of MCT4 profoundly impairs self-renewal and reduces the frequency and tumorigenicity of aggressive, therapy-resistant, glioblastoma stem cells. Mechanistically, we observed that MCT4 depletion induces anaplerotic glutaminolysis and abrogates de novo pyrimidine biosynthesis. The latter results in a dramatic increase in DNA damage and apoptotic cell death, phenotypes that were readily rescued by pyrimidine nucleosides supplementation. Consequently, we found that MCT4 depletion promoted a significant prolongation of survival of animals bearing established orthotopic xenografts, an effect that was extended by adjuvant treatment with focused radiation. Conclusions Our findings establish a novel role for MCT4 as a critical regulator of cellular deoxyribonucleotide levels and provide a new therapeutic direction related to MCT4 depletion in GBM.

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