A WAGR region gene between PAX-6 and FSHB expressed in fetal brain

Schwartz, Faina; Neve, Rachael L.; Eisenman, Robert N.; Gessler, Manfred; Bruns, G. A. P.

doi:10.1007/bf00206960

Cited by 22 publications

(11 citation statements)

References 27 publications

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“…Alternative transcripts are reported in NCBI, but both contain 7 exons, with a variation seen at the 5Ј end of the transcript. Northern blot analysis using human brain RNA showed the highest level of expression of 239FB RNA in the cortex, especially the motor, frontal, and visual cortex (20), with two splice variants showing differential regional expression. A recent report has also shown that although the zebra fish ortholog of 239FB gene is expressed in the brain during development, the amphioxus ortholog was expressed in tissues outside the nervous tissue (47).…”

Section: Discussionmentioning

confidence: 97%

“…The 239FB gene is present between the FSHB and PAX6 genes, and earlier studies have shown that the chromosomal locus of 239FB gene is present within a deletion interval that had been associated with the mental retardation phenotype of WAGR syndrome (19). 239FB mRNA is predominantly expressed in the fetal brain (20), and the high degree of similarity between the predicted protein sequence of 239FB and two Caenorhabditis elegans cDNA clones showed an extensive evolutionary conservation of this protein (21). Although the function of the 239FB protein remains unknown, the distinctive expression of the gene in the fetal brain and the presence of an "ancient conserved region" (21) in this gene suggest its role in the development of the nervous system.…”

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confidence: 99%

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Characterization of an Evolutionarily Conserved Metallophosphoesterase That Is Expressed in the Fetal Brain and Associated with the WAGR Syndrome

Tyagi

Shenoy

Visweswariah

2009

Journal of Biological Chemistry

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Among the human diseases that result from chromosomal aberrations, a de novo deletion in chromosome 11p13 is clinically associated with a syndrome characterized by Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR). Not all genes in the deleted region have been characterized biochemically or functionally. We have recently identified the first Class III cyclic nucleotide phosphodiesterase, Rv0805, from Mycobacterium tuberculosis, which biochemically and structurally belongs to the superfamily of metallophosphoesterases. We performed a large scale bioinformatic analysis to identify orthologs of the Rv0805 protein and identified many eukaryotic genes that included the human 239FB gene present in the region deleted in the WAGR syndrome. We report here the first detailed biochemical characterization of the rat 239FB protein and show that it possesses metallophosphodiesterase activity. Extensive mutational analysis identified residues that are involved in metal interaction at the binuclear metal center. Generation of a rat 239FB protein with a mutation corresponding to a single nucleotide polymorphism seen in human 239FB led to complete inactivation of the protein. A close ortholog of 239FB is found in adult tissues, and biochemical characterization of the 239AB protein demonstrated significant hydrolytic activity against 2,3-cAMP, thus representing the first evidence for a Class III cyclic nucleotide phosphodiesterase in mammals. Highly conserved orthologs of the 239FB protein are found in Caenorhabditis elegans and Drosophila and, coupled with available evidence suggesting that 239FB is a tumor suppressor, indicate the important role this protein must play in diverse cellular events.

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Characterization of an Evolutionarily Conserved Metallophosphoesterase That Is Expressed in the Fetal Brain and Associated with the WAGR Syndrome

Tyagi

Shenoy

Visweswariah

2009

Journal of Biological Chemistry

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“…Mpped2 mRNA is predominantly expressed in fetal brain, 22 NBs analyzed (14/394). 38 The rat fetal brain gene "rat 239FB" is a homolog of human Mpped2, and it has been shown to retain a hydrolytic activity against cAMP, thus representing the first mammalian protein appertaining to the class III cyclic nucleotide metallophosphodiesterases.…”

Section: 21mentioning

confidence: 99%

“…1B), providing support to some previous studies. 22 Some other tissues, such as the thyroid gland, are known to express significant levels of Mpped2. 47 To confirm this specific expression in the CNS, we determined the levels of expression of the murine Mpped2 homolog gene (NM_198778.2) in six mouse tissues at different stages of development (E.14.5, E.16.5, P.0) (Fig.…”

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confidence: 99%

The metallophosphodiesterase Mpped2 impairs tumorigenesis in neuroblastoma

et al. 2012

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“…This locus contains a number of genes such as WT1, BDNF [6], PAX6 [7] (all important during development), FSHB [8], RCN1, and MPPED2 (239FB) [9,10]. MPPED2 mRNA is predominantly expressed in the fetal brain [11] , and our earlier biochemical characterization revealed that this protein belonged to the large family of metallophosphoesterases [9,12]. We could identify orthologs in all mammals and other vertebrates, as well as Caenorhabditis elegans and Drosophila melanogaster [9,12].…”

Section: Introductionmentioning

confidence: 95%

An evolutionarily conserved metallophosphodiesterase is a determinant of lifespan inDrosophila

Gupta

Janardan

Banerjee

et al. 2020

Preprint

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Evolutionarily conserved genes usually have a critical role to play during organismal aging and longevity. Here, we show that a previously uncharacterized Class III metallophosphoesterase in Drosophila, an ortholog of the MPPED1 and MPPED2 proteins in mammals, is necessary for optimal lifespan. dMPPED is the product of the gene CG16717 and hydrolyzed a variety of phosphodiester substrates in a metal-dependent manner. dMPPED was expressed widely during development and in the adult fly. Deletion of the gene in flies dramatically reduced lifespan, without affecting development or fecundity. Longevity was restored on ubiquitous expression of the protein, and neuronal expression of both wild type and the catalytically inactive form of dMPPED was also able to restore normal lifespan. Overexpression of the protein, both ubiquitously and neuronally in wild type flies extended lifespan by ~ 20%. RNA-seq analysis of dMPPED KO flies revealed mis-regulation of innate immune pathways, a number of transcription factors and genes earlier reported to affect aging and lifespan.Importantly, neuronal expression of mammalian MPPED2 was able to rescue lifespan in dMPPED KO flies, but not extend lifespan in wild type flies. This reports the first description of the biological role of an evolutionarily conserved metallophosphoesterase that may serve as a scaffolding protein in diverse signaling pathways to modulate longevity in the fly.

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A WAGR region gene between PAX-6 and FSHB expressed in fetal brain

Cited by 22 publications

References 27 publications

Characterization of an Evolutionarily Conserved Metallophosphoesterase That Is Expressed in the Fetal Brain and Associated with the WAGR Syndrome

Characterization of an Evolutionarily Conserved Metallophosphoesterase That Is Expressed in the Fetal Brain and Associated with the WAGR Syndrome

The metallophosphodiesterase Mpped2 impairs tumorigenesis in neuroblastoma

An evolutionarily conserved metallophosphodiesterase is a determinant of lifespan inDrosophila

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