Neurofibromatosis type 1 (NF1) gene: Implication in neuroectodermal differentiation and genesis of brain tumors

Toru Nishi, Hideyuki Saya

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The gene responsible for neurofibromatosis type 1 (NF1), a common autosomal dominantly inherited disease, has been isolated. A region of NF1 gene product has been demonstrated to share structural and functional similarities with the mammalian GTPase activating protein (GAP) and the yeast IRA proteins. Thus, the NF1 protein is thought to play a role in signal transduction by stimulating the conversion of the Ras protein from a GTP-bound active form to a GDP-bound inactive form. The increased risk of malignant tumors in neuroectodermal tissues of NF1 patients may be caused by disruption of growth and differentiation regulatory functions of the NF1 gene. A second type of the NF1-GAP related domain (NF1-GRD) transcript, which has an extra 21-amino-acid insert in the center of the previously reported first type transcript, has been described. This insert significantly changes the hydrophilicity and secondary structure of the central region of NF1-GRD, therefore, suggesting it also changes its function. Alternative splicing is the most likely mechanism by which these two types of transcripts arise. The NF1-GRD alternative splicing has been shown to be intimately involved in differentiation of neuroectodermal tissues. Aberrant regulation of the alternative splicing may contribute to tumor formation in neuroectodermal tissue.

Original languageEnglish
Pages (from-to)301-310
Number of pages10
JournalCancer and Metastasis Reviews
Volume10
Issue number4
DOIs
Publication statusPublished - 1991 Dec
Externally publishedYes

Fingerprint

Neurofibromatosis 1 Genes
Neurofibromatosis 1
Brain Neoplasms
Alternative Splicing
Neurofibromin 1
GTPase-Activating Proteins
Neuroectodermal Tumors
Neurofibromatosis 2
ras Proteins
Fungal Proteins
Guanosine Triphosphate
Hydrophobic and Hydrophilic Interactions
Signal Transduction
Amino Acids
Growth

Keywords

  • alternative splicing
  • brain tumor
  • neurofibromatosis type 1 gene (NF1 gene)
  • neuronal differentiation
  • NF1-GAP related domain (NF1-GRD)
  • signal transduction

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Neurofibromatosis type 1 (NF1) gene : Implication in neuroectodermal differentiation and genesis of brain tumors. / Nishi, Toru; Saya, Hideyuki.

In: Cancer and Metastasis Reviews, Vol. 10, No. 4, 12.1991, p. 301-310.

Research output: Contribution to journalArticle

@article{2113cc824ae04e8699e45a1ef8ae5c86,
title = "Neurofibromatosis type 1 (NF1) gene: Implication in neuroectodermal differentiation and genesis of brain tumors",
abstract = "The gene responsible for neurofibromatosis type 1 (NF1), a common autosomal dominantly inherited disease, has been isolated. A region of NF1 gene product has been demonstrated to share structural and functional similarities with the mammalian GTPase activating protein (GAP) and the yeast IRA proteins. Thus, the NF1 protein is thought to play a role in signal transduction by stimulating the conversion of the Ras protein from a GTP-bound active form to a GDP-bound inactive form. The increased risk of malignant tumors in neuroectodermal tissues of NF1 patients may be caused by disruption of growth and differentiation regulatory functions of the NF1 gene. A second type of the NF1-GAP related domain (NF1-GRD) transcript, which has an extra 21-amino-acid insert in the center of the previously reported first type transcript, has been described. This insert significantly changes the hydrophilicity and secondary structure of the central region of NF1-GRD, therefore, suggesting it also changes its function. Alternative splicing is the most likely mechanism by which these two types of transcripts arise. The NF1-GRD alternative splicing has been shown to be intimately involved in differentiation of neuroectodermal tissues. Aberrant regulation of the alternative splicing may contribute to tumor formation in neuroectodermal tissue.",
keywords = "alternative splicing, brain tumor, neurofibromatosis type 1 gene (NF1 gene), neuronal differentiation, NF1-GAP related domain (NF1-GRD), signal transduction",
author = "Toru Nishi and Hideyuki Saya",
year = "1991",
month = "12",
doi = "10.1007/BF00554792",
language = "English",
volume = "10",
pages = "301--310",
journal = "Cancer and Metastasis Reviews",
issn = "0167-7659",
publisher = "Springer Netherlands",
number = "4",

}

TY - JOUR

T1 - Neurofibromatosis type 1 (NF1) gene

T2 - Implication in neuroectodermal differentiation and genesis of brain tumors

AU - Nishi, Toru

AU - Saya, Hideyuki

PY - 1991/12

Y1 - 1991/12

N2 - The gene responsible for neurofibromatosis type 1 (NF1), a common autosomal dominantly inherited disease, has been isolated. A region of NF1 gene product has been demonstrated to share structural and functional similarities with the mammalian GTPase activating protein (GAP) and the yeast IRA proteins. Thus, the NF1 protein is thought to play a role in signal transduction by stimulating the conversion of the Ras protein from a GTP-bound active form to a GDP-bound inactive form. The increased risk of malignant tumors in neuroectodermal tissues of NF1 patients may be caused by disruption of growth and differentiation regulatory functions of the NF1 gene. A second type of the NF1-GAP related domain (NF1-GRD) transcript, which has an extra 21-amino-acid insert in the center of the previously reported first type transcript, has been described. This insert significantly changes the hydrophilicity and secondary structure of the central region of NF1-GRD, therefore, suggesting it also changes its function. Alternative splicing is the most likely mechanism by which these two types of transcripts arise. The NF1-GRD alternative splicing has been shown to be intimately involved in differentiation of neuroectodermal tissues. Aberrant regulation of the alternative splicing may contribute to tumor formation in neuroectodermal tissue.

AB - The gene responsible for neurofibromatosis type 1 (NF1), a common autosomal dominantly inherited disease, has been isolated. A region of NF1 gene product has been demonstrated to share structural and functional similarities with the mammalian GTPase activating protein (GAP) and the yeast IRA proteins. Thus, the NF1 protein is thought to play a role in signal transduction by stimulating the conversion of the Ras protein from a GTP-bound active form to a GDP-bound inactive form. The increased risk of malignant tumors in neuroectodermal tissues of NF1 patients may be caused by disruption of growth and differentiation regulatory functions of the NF1 gene. A second type of the NF1-GAP related domain (NF1-GRD) transcript, which has an extra 21-amino-acid insert in the center of the previously reported first type transcript, has been described. This insert significantly changes the hydrophilicity and secondary structure of the central region of NF1-GRD, therefore, suggesting it also changes its function. Alternative splicing is the most likely mechanism by which these two types of transcripts arise. The NF1-GRD alternative splicing has been shown to be intimately involved in differentiation of neuroectodermal tissues. Aberrant regulation of the alternative splicing may contribute to tumor formation in neuroectodermal tissue.

KW - alternative splicing

KW - brain tumor

KW - neurofibromatosis type 1 gene (NF1 gene)

KW - neuronal differentiation

KW - NF1-GAP related domain (NF1-GRD)

KW - signal transduction

UR - http://www.scopus.com/inward/record.url?scp=0026318539&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026318539&partnerID=8YFLogxK

U2 - 10.1007/BF00554792

DO - 10.1007/BF00554792

M3 - Article

C2 - 1786631

AN - SCOPUS:0026318539

VL - 10

SP - 301

EP - 310

JO - Cancer and Metastasis Reviews

JF - Cancer and Metastasis Reviews

SN - 0167-7659

IS - 4

ER -