Identification of a human homolog of the Drosophila neuralized gene within the 10q25.1 malignant astrocytoma deletion region

Nakamura, Hideo; Yoshida, Mitsuhiro; Tsuiki, Hiromasa; Ito, Kota; Ueno, Makoto; Nakao, Mitsuyoshi; Oka, Koji; Tada, Mitsuhiro; Kochi, Masato; Kuratsu, Jun Ichi; Ushio, Yukitaka; Saya, Hideyuki

doi:10.1038/sj.onc.1201618

Cited by 67 publications

(59 citation statements)

References 22 publications

(28 reference statements)

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“…It is found in a wide variety of functionally distinct proteins and may act as a novel protein-interaction module. Evolutionary conservation of the C-terminal C3HC4 RING zinc finger domain is underscored by the sequences of one Caenorhabditis elegans neuralized homolog (C-Neu) in database, which bears a similar extent of homology to M-Neu1 as does D-Neu, and a human homolog of Drosophila neuralized reported recently (27), which is 94% identical to M-Neu1 at the amino acid level. These data suggest that neuralized is an evolutionarily conserved molecule.…”

Section: Resultsmentioning

confidence: 99%

Ethanol hypersensitivity and olfactory discrimination defect in mice lacking a homolog of Drosophila neuralized

Ruan

Tecott

Jiang

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Neurogenic genes in the Notch receptor-mediated signaling pathway play important roles in neuronal cell fate specification as well as neuronal differentiation. The Drosophila neuralized gene is one of the neurogenic genes. We have cloned a mouse homolog of Drosophila neuralized, m-neu1, and found that the m-neu1 transcript is expressed in differentiated neurons. Mice deficient for m-neu1 are viable and morphologically normal, but exhibit specific defects in olfactory discrimination and hypersensitivity to ethanol. These findings reveal an essential role of m-neu1 in ensuring proper processing of certain information in the adult brain.M any molecular mechanisms controlling neural development and neural function are evolutionarily conserved (1-3). One example is the Notch-mediated cell-cell interaction, a mechanism to mediate signaling between adjacent cells and thereby to specify cell fates in organisms ranging from worms and flies to mammals (4). In a given organism, the Notch signaling mechanism functions in many developmental processes as well as in adult life (5, 6). In the nervous system, the Notch signaling mechanism is involved in neurogenesis (1, 3), neuronal differentiation (2, 6), axon path finding (7,8), and neurite growth (9, 10). The importance of Notch in maintaining normal neuronal function in the adult has been revealed by a number of human neurological syndromes because of defects in Notch signaling (6).Like Notch, the Drosophila neuralized gene (neu) is a neurogenic gene whose function is to limit the number of neuronal precursor cells and to specify sensory organ as well as R8 photoreceptor cell fates (11)(12)(13)(14)(15)(16)(17). Genetic analyses suggest that neuralized interacts with other neurogenic genes, such as the Notch receptor and the Delta ligand for cell-cell interaction (18). Recent studies (15)(16)(17) revealed that neuralized functions cellautonomously to regulate a subset of Notch-dependent processes. How neuralized affects Notch signaling is unknown at present. An interesting possibility is that Neu protein with its C3HC4 RING finger domain functions as an E3 ubiquitin ligase to modulate Notch signaling (15)(16)(17)19).We have cloned a mouse homolog of Drosophila neuralized, m-neu1, and found that it is expressed in differentiated neurons. We examined its functional role in the nervous system by generating a loss-of-function allele of m-neu1. Whereas the m-neu1 null mutants exhibit normal performance in a number of behavioral tests, including Morris water maze assay for learning and memory, they display specific functional lesions in olfactory discrimination and ethanol effects on motor coordination. These studies identify specific functions of the adult brain that are critically dependent on m-neu1 activity. Materials and MethodsIsolation of a Mouse Neuralized Homolog. A mouse midgestation embryonic cDNA library (Stratagene) was screened with fragments of Drosophila neuralized cDNA as probes. In brief, the duplicated nylon filters containing mouse phage cDNAs were prehybridized...

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Section: Resultsmentioning

confidence: 99%

Ethanol hypersensitivity and olfactory discrimination defect in mice lacking a homolog of Drosophila neuralized

Ruan

Tecott

Jiang

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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“…Indeed, loss-offunction mutations of the neurogenic genes produce hyperplasia of the embryonic nervous system in flies (35), somewhat analogous to the brain phenotype of the brain-specific PTEN knockout mice (36). Furthermore, Neuralized is highly expressed in normal human brain tissue but is low or absent in advanced gliomas (37).…”

Section: Discussionmentioning

confidence: 99%

Insulin growth factor-binding protein 2 is a candidate biomarker for PTEN status and PI3K/Akt pathway activation in glioblastoma and prostate cancer

Mehrian‐Shai

Chen

Shi

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

176

127

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“…The loss-of-function mutation of these genes results in hyperplasia or neoplastic overgrowth in various tissues, leading to the death of these insects (Gate et al, 1989). Several genes which encode for polypeptides homologous to the Drosophila tumor suppressor genes have been identi®ed in mammalian cells, and they have been recently shown to be involved in various cellular events including growth regulation and di erentiation (Makino et al, 1997;Nakamura et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we isolated the ®rst human homolog of the D-l(3)mbt gene, which we designated h-l(3)mbt, by a combination of a computer analysis of the expressed sequenced tag (EST) databases and a twostep polymerase chain reaction (PCR) procedure (Makino et al, 1997;Nakamura et al, 1998). We report here the chromosome location of this gene and its mRNA expression in various human tissues and cancer cells.…”

Section: Introductionmentioning

confidence: 99%

A human homolog of Drosophila lethal(3)malignant brain tumor (l(3)mbt) protein associates with condensed mitotic chromosomes

et al. 1999

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Identification of a human homolog of the Drosophila neuralized gene within the 10q25.1 malignant astrocytoma deletion region

Cited by 67 publications

References 22 publications

Ethanol hypersensitivity and olfactory discrimination defect in mice lacking a homolog of Drosophila neuralized

Ethanol hypersensitivity and olfactory discrimination defect in mice lacking a homolog of Drosophila neuralized

Insulin growth factor-binding protein 2 is a candidate biomarker for PTEN status and PI3K/Akt pathway activation in glioblastoma and prostate cancer

A human homolog of Drosophila lethal(3)malignant brain tumor (l(3)mbt) protein associates with condensed mitotic chromosomes

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