Differential expression of two types of the neurofibromatosis type 1 (NF1) gene transcripts related to neuronal differentiation.
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-GRD 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.
Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
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T
Nishi
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Lee
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Oka
V A
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Levin
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Tanase
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Morino
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Saya
D000595:Amino Acid Sequence; D001254:Astrocytoma; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D020930:MAP Kinase Kinase Kinases; D008969:Molecular Sequence Data; D025542:Neurofibromin 1; D009474:Neurons / Q000166:cytology*; D009838:Oligodeoxyribonucleotides; D015513:Oncogene Proteins; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D011494:Protein Kinases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D004273:DNA, Neoplasm; D025542:Neurofibromin 1; D009838:Oligodeoxyribonucleotides; D015513:Oncogene Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011494:Protein Kinases; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human