Complementary DNA structure and genomic organization of Drosophila menin

Maruyama, Kouji; Tsukada, Toshihiko; Honda, Munehiro; Nara-Ashizawa, Noriko; Noguchi, Kiyoteru; Cheng, Jinyan; Ohkura, Naganari; Sasaki, Kazuki; Yamaguchi, Ken

doi:10.1016/s0303-7207(00)00307-5

Cited by 29 publications

(22 citation statements)

References 17 publications

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“…The amino acid sequence of the menin protein, which exhibits no sequence similarity with any other known proteins, is highly conserved; orthologues have been identified in vertebrates and Drosophila (16)(17)(18)(19)(20), but not in the genomes of yeast or Caenorhabditis elegans. The 610-amino-acid sequence of menin exhibits no identifiable functional motifs, except for two novel and independent carboxyl-terminal nuclear localization signals (21), consistent with its predominantly nuclear distribution (21,22).…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of the Menin Tumor Suppressor Protein on Serine 543 and Serine 583

MacConaill

Hughes

Rozenblatt-Rosen

et al. 2006

Molecular Cancer Research

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Section: Introductionmentioning

confidence: 99%

Phosphorylation of the Menin Tumor Suppressor Protein on Serine 543 and Serine 583

MacConaill

Hughes

Rozenblatt-Rosen

et al. 2006

Molecular Cancer Research

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“…Highly conserved orthologs of the MEN1 gene have been found in a variety of organisms, including molluscs (31), Drosophila (11,26), zebra fish (19,25), rats (18), and mice (29). However, the 610-amino-acid human menin sequence provides few clues to the function of the protein, since it shows no homology to any other protein and has no identifiable functional motifs, except for two functionally independent, C-terminal nuclear localization signals (12).…”

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confidence: 99%

Conditional Inactivation of the Men1 Gene Leads to Pancreatic and Pituitary Tumorigenesis but Does Not Affect Normal Development of These Tissues

Biondi

Gartside

Waring

et al. 2004

Molecular and Cellular Biology

123

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Mutations of the MEN1 gene, encoding the tumor suppressor menin, predispose individuals to the cancer syndrome multiple endocrine neoplasia type 1, characterized by the development of tumors of the endocrine pancreas and anterior pituitary and parathyroid glands. We have targeted the murine Men1 gene by using Cre recombinase-loxP technology to develop both total and tissue-specific knockouts of the gene. Conditional homozygous inactivation of the Men1 gene in the pituitary gland and endocrine pancreas bypasses the embryonic lethality associated with a constitutional Men1 ؊/؊ genotype and leads to ␤-cell hyperplasia in less than 4 months and insulinomas and prolactinomas starting at 9 months. The pituitary gland and pancreas develop normally in the conditional absence of menin, but loss of this transcriptional cofactor is sufficient to cause ␤-cell hyperplasia in some islets; however, such loss is not sufficient to initiate pituitary gland tumorigenesis, suggesting that additional genetic events are necessary for the latter.

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“…(16)(17)(18) Germline mutations of the MEN1 gene Prevalence of mutation in MEN1 and related disorders. Heterozygous germline mutations of the MEN1 gene have been identified in approximately 90% of familial MEN1, in which multiple patients are found in a family, and in a smaller fraction of sporadic MEN1 patients.…”

Section: Structure and Expression Of The Men1 Genementioning

confidence: 99%

“…(12)(13)(14)(15) Menin orthologues have been identified in vertebrates and also invertebrates including fruit fly and snail, but not in the yeast Saccharomyces cerevisiae or nematode Caenorhabditis elegans. (16)(17)(18) Germline mutations of the MEN1 gene Prevalence of mutation in MEN1 and related disorders. Heterozygous germline mutations of the MEN1 gene have been identified in approximately 90% of familial MEN1, in which multiple patients are found in a family, and in a smaller fraction of sporadic MEN1 patients.…”

Section: Structure and Expression Of The Men1 Genementioning

confidence: 99%

MEN1 gene and its mutations: Basic and clinical implications

Tsukada¹,

Nagamura²,

Ohkura³

2009

Cancer Science

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Heterozygous germline mutations of the tumor-suppressor gene MEN1 are responsible for multiple endocrine neoplasia type 1 (MEN1), a dominantly inherited familial cancer syndrome characterized by pituitary, parathyroid, and enteropancreatic tumors. Various mutations have been identified throughout the entire gene region in patients with MEN1 and related disorders. Neither mutation hot spot nor phenotype-genotype correlation has been established in MEN1 although some missense mutations may be specifically associated with a phenotype of familial isolated hyperparathyroidism. The gene product menin has been implicated in multiple roles, including gene transcription, maintenance of genomic integrity, and control of cell division and differentiation. These multiple functions are likely to be conferred by association with multiple protein factors. Occurrence of MEN1-causing missense mutations throughout menin also suggests the requirement of multiple binding factors for its full tumor-suppressive activity. The effect of menin depletion is highly tissue specific, but its underlying mechanism remains to be elucidated. A DNA test for MEN1 germline mutations is a useful tool for diagnosis of MEN1 although it needs further improvements. The germline mutations are heterozygous, and somatic loss of the normal MEN1 allele has been observed in the tumors arising in MEN1, in agreement with the Knudson's two-hit model. (11) Somatic inactivation of both MEN1 alleles has also been detected in some sporadic endocrine tumors, indicating involvement of this gene in the development of sporadic tumors. So far, MEN1 gene mutations have not been implicated in any other human diseases.The product of the MEN1 gene, menin, is a 610-amino acid protein that exhibits no apparent sequence similarity to any other known protein.(1) Thus, its biochemical function can not be deduced from its structure. In the last decade, a number of studies have demonstrated physical and functional associations between menin and diverse proteins of known function, shedding light on its molecular function. These menin-interacting proteins include nuclear proteins such as transcription factors, histone deacetylases, and histone methyltransferases, suggesting that menin is involved in gene transcription. Several lines of evidence also suggest that menin is involved in the maintenance of genomic integrity. Although menin is localized mainly to cell nuclei, possible extranuclear functions have not been excluded because various cytoplasmic proteins bind to menin.Although the molecular function of menin is still poorly understood, identification of the MEN1 gene has enabled a direct DNA test for predisposition to MEN1. In the present review, recent findings on the MEN1 gene are summarized and its mutations are discussed from basic and clinical points of view. Structure and expression of the MEN1 geneThe human MEN1 gene comprises 10 exons distributed over 7 kb in the chromosome region 11q13 and encodes mRNA of approximately 2.8 kb (Fig. 2).(1) Exons 2 through 10 encode th...

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Complementary DNA structure and genomic organization of Drosophila menin

Cited by 29 publications

References 17 publications

Phosphorylation of the Menin Tumor Suppressor Protein on Serine 543 and Serine 583

Phosphorylation of the Menin Tumor Suppressor Protein on Serine 543 and Serine 583

Conditional Inactivation of the Men1 Gene Leads to Pancreatic and Pituitary Tumorigenesis but Does Not Affect Normal Development of These Tissues

MEN1 gene and its mutations: Basic and clinical implications

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