cDNA cloning of the type 1 neurofibromatosis gene: Complete sequence of the NF1 gene product

Marchuk, Douglas A.; Saulino, Ann M.; Tavakkol, Roxanne; Swaroop, Manju; Wallace, Margaret R.; Andersen, Lone B.; Mitchell, Anna L.; Gutmann, David H.; Boguski, Mark S.; Collins, Francis S.

doi:10.1016/0888-7543(91)90017-9

Cited by 374 publications

(236 citation statements)

References 56 publications

(24 reference statements)

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“…All experiments were repeated with two affinity purified polyclonal antibodies; PC(772-1085) and PC(2435-2754) raised against TrpE fusion proteins representing amino acids 772-1085 and 2435-2754 of neurofibromin, respectively (nomenclature according to Marchuk et al, 1991). Peptides outside the GAP-homology domain were chosen to avoid generating antibodies that could cross-react with GAP or GAP-like proteins.…”

Section: Experimental Procedures Antibodiesmentioning

confidence: 99%

“…Neurofibromin is a 220-250 kDa protein DeClue et al, 1991;Hattori et al, 1991;Daston et al, 1992). Cloning and sequencing of the NF1 gene (Wallace et al, 1990;Viskochil et al, 1990;Cawthon et al, 1990;Buchberg et al, 1990;Xu et al, 1990b;Marchuk et al, 1991) revealed sequence homology to GTPase activating proteins (GAPS). These proteins can act as negative regulators of the protooncogene product Ras by facilitating the GTPase activity of Ras and thus increasing the proportion of the inactivated GDP-bound form of Ras in a cell (Bollag and McCormick, 1991).…”

Section: Introductionmentioning

confidence: 99%

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Neurofibromin, a predominantly neuronal GTPase activating protein in the adult, is ubiquitously expressed during development

Daston

Ratner

1992

Developmental Dynamics

105

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The onset of manifestations of the common, autosomal dominantly inherited disease type 1 neurofibromatosis (NFl) is usually in childhood. To begin to understand the pathogenesis of NF1, we analyzed the developmental pattern of expression of the protein product of the NF1 gene, neurofibromin, by Western blotting and immunohistochemistry using the rat as a model system. Neurofibromin is uniformly distributed throughout embyronic day 10 and 12 rat embryos. By embryonic day 16, neurofibromin immunoreactivity is enriched in neurons of the cortical plate, in peripheral ganglia, and in developing CNS and PNS fiber tracts, but remains detectable outside the nervous system. Expression decreases in nonneural tissues by postnatal day 6, and neurofibromin is greatly decreased (lung, adrenal cortex, skin) or absent (skeletal muscle, cartilage) in adult tissues except for brain, spinal cord, peripheral nerve, and adrenal medulla. Transient expression of neurofibromin during development in many tissues suggests the importance of this GTPase-activating protein in morphogenesis and organ growth. A separate role is proposed for neurofibromin in growing axons and in the mature nervous system. 0 1993 Wiley-Liss, Inc.

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Section: Experimental Procedures Antibodiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neurofibromin, a predominantly neuronal GTPase activating protein in the adult, is ubiquitously expressed during development

Daston

Ratner

1992

Developmental Dynamics

105

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“…Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1 gene, which encodes the tumor suppressor neurofibromin Viskochil et al, 1990;Marchuk et al, 1991]. People with NF1 are constitutionally heterozygous for an NF1 loss-of-function mutation, that is, they are haploinsufficient for NF1.…”

Section: Introductionmentioning

confidence: 99%

Skeletal abnormalities in neurofibromatosis type 1: Approaches to therapeutic options

Elefteriou

Kolanczyk

Schindeler

et al. 2009

American J of Med Genetics Pt A

131

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The skeleton is frequently affected in individuals with neurofibromatosis type 1, and some of these bone manifestations can result in significant morbidity. The natural history and pathogenesis of the skeletal abnormalities of this disorder are poorly understood and consequently therapeutic options for these manifestations are currently limited. The Children's Tumor Foundation convened an International Neurofibromatosis Type 1 Bone Abnormalities Consortium to address future directions for clinical trials in skeletal abnormalities associated with this disorder. This report reviews the clinical skeletal manifestations and available preclinical mouse models and summarizes key issues that present barriers to optimal clinical management of skeletal abnormalities in neurofibromatosis type 1. These concepts should help advance optimal clinical management of the skeletal abnormalities in this disease and address major difficulties encountered for the design of clinical trials. © 2009 Wiley‐Liss, Inc.

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“…The disorder is characterized by tumors of the peripheral nervous system and developmental abnormalities including multiple tumors of various origins which a ect several organ systems (Riccardi, 1981). The NF1 gene, ®rst mapped in 1987 (Barker et al, 1987;Goldgar et al, 1987;Seizinger et al, 1987), is a 300 ± 350 kilobase gene encoding at least 2818 amino acides which maps to chromosome 17q (Marchuk et al, 1991). NF1 is commonly accepted as one of several known tumor suppressor genes (Skuse and Ludlow, 1995).…”

mentioning

confidence: 99%

Differential expression of NF1 type I and type II isoforms in sporadic borderline and invasive epithelial ovarian tumors

Iyengar

Lau

et al. 1999

Oncogene

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The NF1 gene, a putative tumor suppressor gene, contains a GAP related domain (GRD) which accelerates hydrolysis of ras-bound GTP to GDP, thereby converting the ras oncogene from its active to inactive form. Two forms of the NF1 GRD transcript (Type I and Type II) are di erentially expressed in neuroectodermal tumor tissue relative to di erentiated neural cells, and in gastric cancer cell lines relative to normal stomach mucosa. We measured relative expression of NF1 Type II and Type I isoforms in cultured normal and malignant human ovarian surface epithelial cells(HOSE) and in invasive and borderline ovarian tumor tissue. We demonstrated an 11-fold increase in Type II: Type I ratio in 7 HOSE cultures relative to eight ovarian cancer cell lines. Our ®ndings indicate a signi®cant decrease in Type II isoform expression and increase in Type I expression in ovarian cancer cells and tumor tissue relative to HOSE cells. We also demonstrate an increase in Type II: Type I ratio, and a decrease in cell proliferation rate in three ovarian cancer cell lines on treatment with retinoic acid. We propose that di erential expression of the NF1 Type I and Type II isoforms is related to cellular di erentiation in ovarian epithelial cancer and strategies based on alteration in NF1 isoform expression may have therapeutic potential in ovarian malignancies.Keywords: ovary; cancer; NF1; retinoic acid Ovarian cancer is the ®fth most common cancer and the fourth leading cause of cancer death among women in the United States. It is the leading cause of death by gynecologic malignancy. While much of our understanding of the genetic basis of ovarian cancer remains speculative, evidence indicates that development of ovarian tumors requires a series of genetic changes involving dominant oncogenes, mismatch repair genes, and a large number of tumor suppressor genes (Cliby et al

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cDNA cloning of the type 1 neurofibromatosis gene: Complete sequence of the NF1 gene product

Cited by 374 publications

References 56 publications

Neurofibromin, a predominantly neuronal GTPase activating protein in the adult, is ubiquitously expressed during development

Neurofibromin, a predominantly neuronal GTPase activating protein in the adult, is ubiquitously expressed during development

Skeletal abnormalities in neurofibromatosis type 1: Approaches to therapeutic options

Differential expression of NF1 type I and type II isoforms in sporadic borderline and invasive epithelial ovarian tumors

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