Neurofibromatosis type 1 tumour suppressor gene expression is deficient in psoriatic skin in vivo and in vitro: a potential link to increased Ras activity

2004 ◽  
Vol 150 (2) ◽  
pp. 211-219 ◽  
Author(s):  
S-L. Karvonen ◽  
J. Koivunen ◽  
M. Nissinen ◽  
H. Yla-Outinen ◽  
A-S. Bjorkstrand ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Psoriatic Skin ◽  
Potential Link

scholarly journals TATA-Binding Protein (TBP)-Like Factor (TLF) Is a Functional Regulator of Transcription: Reciprocal Regulation of the Neurofibromatosis Type 1 and c-fos Genes by TLF/TRF2 and TBP

2005 ◽  
Vol 25 (7) ◽  
pp. 2632-2643 ◽  
Author(s):  
Jayhong A. Chong ◽  
Magdalene M. Moran ◽  
Martin Teichmann ◽  
J. Stefan Kaczmarek ◽  
Robert Roeder ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Binding Protein ◽  
Neurofibromatosis Type ◽  
Tata Binding Protein ◽  
Related Factor ◽  
Reciprocal Regulation ◽  
In Cells

ABSTRACT The lack of direct targets for TATA-binding protein (TBP)-like factors (TLFs) confounds the understanding of their role in gene expression. Here we report that human TLF (also called TBP-related factor 2 [TRF2]) activates a number of different genes, including the neurofibromatosis type 1 (NF1) gene. The overexpression of TLF increases the amount of NF1 mRNA in cells. In vivo, TLF binds to and upregulates transcription from a fragment of the NF1 promoter. In vitro, purified TLF-TFIIA binds directly to the same NF1 promoter fragment that is required for TLF responsiveness in cells. Furthermore, targeted deletion of TLF in mice reduces NF1 levels. In contrast, TLF inhibits transcription driven by a fragment from the TATA-containing c-fos promoter by sequestering TFIIA. TBP affects the NF1 and c-fos promoters in a manner reciprocal to that of TLF, stimulating the c-fos promoter and inhibiting NF1 transcription. We conclude that TLF is a functional regulator of transcription with targets distinct from those of TBP.

Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumour suppressor gene hypothesis

1993 ◽  
Vol 3 (2) ◽  
pp. 122-126 ◽  
Author(s):  
Eric Legius ◽  
Douglas A. Marchuk ◽  
Francis S. Collins ◽  
Thomas W. Glover
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor

Mutations of the NF1 Gene in Children With Juvenile Myelomonocytic Leukemia Without Clinical Evidence of Neurofibromatosis, Type 1

Blood ◽  
1998 ◽  
Vol 92 (1) ◽  
pp. 267-272 ◽  
Author(s):  
Lucy E. Side ◽  
Peter D. Emanuel ◽  
Brigit Taylor ◽  
Janet Franklin ◽  
Patricia Thompson ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Juvenile Myelomonocytic Leukemia ◽  
Translation System ◽  
Polymorphism Analysis ◽  
Single Stranded Conformational Polymorphism ◽  
Myelomonocytic Leukemia

Juvenile myelomonocytic leukemia (JMML) is a pediatric myelodysplastic syndrome that is associated with neurofibromatosis, type 1 (NF1). The NF1 tumor suppressor gene encodes neurofibromin, which regulates the growth of immature myeloid cells by accelerating guanosine triphosphate hydrolysis on Ras proteins. The purpose of this study was to determine if the NF1gene was involved in the pathogenesis of JMML in children without a clinical diagnosis of NF1. An in vitro transcription and translation system was used to screen JMML marrows from 20 children for NF1mutations that resulted in a truncated protein. Single-stranded conformational polymorphism analysis was used to detect RASpoint mutations in these samples. We confirmed mutations of NF1in three leukemias, one of which also showed loss of the normalNF1 allele. An NF1 mutation was detected in normal tissue from the only patient tested and this suggests that JMML may be the presenting feature of NF1 in some children. Activating RASmutations were found in four patients; as expected, none of these samples harbored NF1 mutations. Because 10% to 14% of children with JMML have a clinical diagnosis of NF1, these data are consistent with the existence of NF1 mutations in approximately 30% of JMML cases.

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