Disease relevance of NF1

• Bovine cutaneous neurofibromatosis is a naturally occurring disease in this group of animals, characterized by skin tumors morphologically identical to those of NF1 [1].
• All cutaneous lesions but one were consistent with neurofibromas in noncutaneous sites in cattle and neurofibromas in patients with NF1 [1].
• A consecutive series of six meningiomas and one meningioma/neurofibroma derived from a patient with neurofibromatosis type 2 was investigated and it was found that the growth of all seven tumours in response to mitotic stimuli (fetal bovine serum or epidermal growth factor) is strongly inhibited by IFN-alpha [2].

High impact information on NF1

• cDNA walking and sequencing have extended the open reading frame for the neurofibromatosis type 1 gene (NF1) [3].
• Base substitution mutations of the NF1 binding site abolished the NF1-DNA interaction [4].
• An NF1-like protein functions as a repressor of the von Willebrand factor promoter [4].
• These analyses demonstrated that an NF1-like protein interacts with DNA sequences spanning -440 to -470 nucleotides in the negative regulatory region of the vWf promoter [4].
• Two distinct GAPs of 120 and 235 kDa called GAP1 and NF1 serve as attenuators of Ras, a member of GTP-dependent signal transducers, by stimulating its intrinsic guanosine triphosphatase (GTPase) activity [5].

Biological context of NF1

• In contrast, the mean intron identities around the alternatively skipped exons in CTFR and NF1 do not differ considerably from those around the constitutive exons [6].
• In contrast, we found on average high conservation of intron sequences over 300 base pairs up- and downstream of the five alternatively included NF1 exons [6].
• The neurofibromatosis 1 (NF1) gene encodes a cytoplasmic protein with structural and functional homology to GTPase activating proteins (GAPs) for p21-ras [7].
• Following remodelling and in the presence of NF1, which maintains the open nucleosome conformation, additional PR molecules bind, transactivation takes place and H1 is displaced from the promoter during transcription initiation [8].
• An electrophoretic mobility shift assay with nuclear proteins derived from rabbit mammary glands showed changes in the patterns of Stat5, MAF, NF1 and Oct1 DNA-protein binding during progression of pregnancy and transition to lactation [9].

Anatomical context of NF1

• Double-labeling immunofluorescence experiments using neurofibromin antibodies and in vitro microtubule assembly have demonstrated that the NF1 gene product, neurofibromin, interacts with cytoplasmic microtubules [7].
• The skin fibroblasts from neurofibromatosis type 1 patients, and normal subjects were brought into the quiescent state by serum-starvation, and after the re-addition of the serum, the recovery to cycling states were analysed by flow cytometry [10].

Associations of NF1 with chemical compounds

• Further sequence analysis revealed the presence of several eukaryotic transcriptional elements such as NF-E1, Poly-A signal, lariat consensus sequences, and CTF/NF1 binding sites [11].
• Antibody against neurofibromatosis type 1 gene product reacts with a triton-insoluble GTPase activating protein toward ras p21 [12].

References