Differential expression of two types of the neurofibromatosis type 1 (NF1) gene transcripts related to neuronal differentiation

Toru Nishi, Polly S Y Lee, Koji Oka, Victor A. Levin, Sumio Tanase, Yoshimasa Morino, Hideyuki Saya

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

A 360 residue region encoded by the neurofibromatosis type 1 (NF1) gene shows significant homology to the catalytic domains of both mammalian GTPase-activating proteins (GAP) and yeast IRA proteins. This GAP-related domain of the NF1 gene (NF1-GRD), like the GAP and IRA protein, has been reported to mediate hydrolysis of Ras-bound GTP to GDP, resulting in inactivation of Ras protein. In the present study, we identified two different types of NF1-GRD cDNA. One (type I) is identical to the previously reported sequence, and the other (type II) contained an additional 63 bp insertion that encodes for a region of 21 amino acids in the center of the NF1-GRO molecule. Alternative splicing is the most likely mechanism by which these two types of transcripts arise. Our observations reveal that the type I transcript is predominantly expressed in undifferentiated cells, whereas the type II transcript predominates in differentiated cells. Furthermore, the expression pattern of type I and type II NF1-GRD mRNA immediately changed in SH-SY5Y neuroblastoma cells when neuronal differentiation programs were induced by retinoic acid treatment. We propose that the differential expression of type I and type II NF1-GRD transcripts might be an 'on/off' switch that regulates the catalytic activity of the NF1 gene product, which plays an important role in the regulation of neuronal differentiation.

Original languageEnglish
Pages (from-to)1555-1559
Number of pages5
JournalOncogene
Volume6
Issue number9
Publication statusPublished - 1991 Sep
Externally publishedYes

Fingerprint

Neurofibromatosis 1 Genes
Neurofibromatosis 1
GTPase-Activating Proteins
Neurofibromatosis 2
Neurofibromin 1
ras Proteins
Fungal Proteins
Alternative Splicing
Guanosine Triphosphate
Tretinoin
Neuroblastoma
Catalytic Domain
Hydrolysis
Complementary DNA

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Nishi, T., Lee, P. S. Y., Oka, K., Levin, V. A., Tanase, S., Morino, Y., & Saya, H. (1991). Differential expression of two types of the neurofibromatosis type 1 (NF1) gene transcripts related to neuronal differentiation. Oncogene, 6(9), 1555-1559.

Differential expression of two types of the neurofibromatosis type 1 (NF1) gene transcripts related to neuronal differentiation. / Nishi, Toru; Lee, Polly S Y; Oka, Koji; Levin, Victor A.; Tanase, Sumio; Morino, Yoshimasa; Saya, Hideyuki.

In: Oncogene, Vol. 6, No. 9, 09.1991, p. 1555-1559.

Research output: Contribution to journalArticle

Nishi, T, Lee, PSY, Oka, K, Levin, VA, Tanase, S, Morino, Y & Saya, H 1991, 'Differential expression of two types of the neurofibromatosis type 1 (NF1) gene transcripts related to neuronal differentiation', Oncogene, vol. 6, no. 9, pp. 1555-1559.
Nishi, Toru ; Lee, Polly S Y ; Oka, Koji ; Levin, Victor A. ; Tanase, Sumio ; Morino, Yoshimasa ; Saya, Hideyuki. / Differential expression of two types of the neurofibromatosis type 1 (NF1) gene transcripts related to neuronal differentiation. In: Oncogene. 1991 ; Vol. 6, No. 9. pp. 1555-1559.
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