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 language | English |
|---|---|
| Pages (from-to) | 301-310 |
| Number of pages | 10 |
| Journal | Cancer and Metastasis Reviews |
| Volume | 10 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1991 Dec |
| Externally published | Yes |
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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 journal › Article
}
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 -