Control of drosopterin synthesis in Drosophila melanogaster: Mutants showing an altered pattern of GTP cyclohydrolase activity during development

Evans, Bronwyn A; Howells, A. J.

doi:10.1007/bf00484381

Cited by 39 publications

(12 citation statements)

References 19 publications

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“…Consistent with the expression profile of GTPCH I, Drosophila exhibits a characteristic activity profile of GTPCH I during the life cycle (25, 26). Two peaks of GTPCH I activity occur during development.…”

Section: Enzymesmentioning

confidence: 60%

Biosynthesis of drosopterins, the red eye pigments of Drosophila melanogaster

Kim

Yim

2013

IUBMB Life

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Drosophila melanogaster has red eyes. Scientists have been curious about the biosynthesis of the red eye pigments and have completed a number of investigations on these compounds. Scientific contributions made over the past 50 years have improved our understanding of the red eye pigments. Researchers have elucidated the chemical structures of some pigments and have successfully purified and identified the enzymes that participate in the biosynthesis of the red eye pigments. In this article, we will review the characteristics of the Drosophila red eye pigments and of the enzymes and genes involved in its biosynthetic pathway. V C 2013 IUBMB Life, 65(4): [334][335][336][337][338][339][340] 2013

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Section: Enzymesmentioning

confidence: 60%

Biosynthesis of drosopterins, the red eye pigments of Drosophila melanogaster

Kim

Yim

2013

IUBMB Life

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“…The first and rate-limiting step in pteridine synthesis is catalyzed by the enzyme GTP cyclohydrolase (GTPCH), which converts substrate GTP to dihydroneopterine triphosphate (39). It has been shown that in pn mutants the pteridine level is reduced and the activity levels of GTPCH becomes variable (40). Since Nm23/Awd as a NDPK is presumed to supply nucleoside triphosphate, thus driving the forward reaction catalyzed by GTPCH, the defects in pn mutants are consistent with the genetic data that implicate Pn as an antagonist of Nm23/Awd.…”

Section: The Function Of Pnmentioning

confidence: 99%

Developmental function of Nm23/awd: a mediator of endocytosis

2009

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The metastasis suppressor gene Nm23 is highly conserved from yeast to human, implicating a critical developmental function. Studies in cultured mammalian cells have identified several potential functions, but many have not been directly verified in vivo. Here we summarize the studies on the Drosophila homologue of the Nm23 gene, named abnormal wing discs (awd), which shares 78% amino acid identity with the human Nm23-H1 and H2 isoforms. These studies confirmed that awd gene encodes a nucleoside diphosphate kinase, and provided strong evidence of a role for awd in regulating cell differentiation and motility via regulation of growth factor receptor signaling. The latter function is mainly mediated by control of endocytosis. This review provides a historical account of the discovery and subsequent analyses of the awd gene. We will also discuss the possible molecular function of the Awd protein that underlies the endocytic function. KeywordsNm23; awd; prune; Killer-of-prune; Drosophila Nm23 was first isolated as a cDNA clone that was down-regulated in highly metastatic derivatives of murine melanoma cell line K-1735 (1). The gene is highly conserved in the eukaryotes from yeast to mammals. In vertebrates it consists of a gene family of eight.Nm23 has been shown to inhibit metastasis, but not primary tumor growth, in xenografts of cells from human breast cancer, murine melanoma, rat colon cancer and human oral squamous cancer (2). However, in clinical cancer samples, this correlation is much weaker. While in initial breast cancer studies reduced Nm23 expression levels were consistent with increased metastasis (3), in later studies no clear correlation could be discerned when comparing benign tumors and metastatic cancers (4-8). It has become clear that Nm23 plays a critical role in normal tissue functions, and both up-and down-regulation of this gene can disrupt growth and differentiation. The function of Nm23Further complicating the issue of Nm23's role in tumor progression is the multiple enzymatic functions assigned to Nm23: (a) Nucleoside diphosphate kinase (NDPK) that transfers the terminal phosphate group from ATP to a non-ATP nucleoside diphosphate (such as GDP), through the formation of an intermediate histidine-phosphate linkage at histidine 118 (residue 119 in Drosophila) (2). (b) DNA binding and DNA nuclease that is involved in transcriptional regulation (9,10). (c) DNase activity that is activated by granzyme A in caspase-independent apoptosis (11). (d) Histidine-dependent protein kinase (12)(13)(14). This enzymatic activity is similar to that of NDPK but toward protein substrates (15). Some tantalizing kinase targets have been identified such as aldolase C and kinase suppressor of Ras (Ksr), but the in vivo relevance of which requires further investigation (16). It is therefore critical that the apparently complex Nm23 functions be examined in physiologically relevant model systems. The Drosophila model to date has provided the most extensive set of studies, in part because Drosophila genome enc...

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“…hs-FLP and w1118 , were compared. Pigment concentrations were determined at 485 nm, as described by Evans and Howells (38). …”

Section: Methodsmentioning

confidence: 99%

Idefix insulator activity can be modulated by nearby regulatory elements

Brasset¹,

Bantignies²,

Court³

et al. 2007

Nucleic Acids Research

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Insulators play important roles in controlling gene activity and maintaining regulatory independence between neighbouring genes. In this article, we show that the enhancer-blocking activity of the insulator present within the LTR retrotransposon Idefix can be abolished if two copies of the region containing the insulator—specifically, the long terminal repeat (LTR)—are fused to the retrotransposon's 5′ untranslated region (5′ UTR). The presence of this combination of two [LTR-5′ UTR] modules is a prerequisite for the loss of enhancer-blocking activity. We further show that the 5′ UTR causes flanking genomic sequences to be displaced to the nuclear periphery, which is not observed when two insulators are present by themselves. This study thus provides a functional link between insulators and independent genomic modules, which may cooperate to allow the specific regulation of defined genomic loci via nuclear repositioning. It further illustrates the complexity of genomic regulation within a chromatic environment with multiple functional elements.

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Control of drosopterin synthesis in Drosophila melanogaster: Mutants showing an altered pattern of GTP cyclohydrolase activity during development

Cited by 39 publications

References 19 publications

Biosynthesis of drosopterins, the red eye pigments of Drosophila melanogaster

Biosynthesis of drosopterins, the red eye pigments of Drosophila melanogaster

Developmental function of Nm23/awd: a mediator of endocytosis

Idefix insulator activity can be modulated by nearby regulatory elements

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