Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to understand the mechanism of oncogenic activation, we have analyzed the c-raf-1 gene from the GL-5-JCK human glioblastoma, which underwent rearrangement during transfection experiments. Nucleotide sequencing of cDNA clones derived from the 2.5 kb raf-mRNA, which is a major transcript of raf in NIH3T3 cells transformed with GL-5-JCK DNA, revealed that this mRNA contains sequences derived from the human c-raf-1 gene and the human lipocortin II gene. Translation of the 2.5 kb raf-mRNA predicted a fusion protein consisting of 16 amino-terminal amino acid residues of the lipocortin II and 370 carboxy-terminal amino acid residues of the c-raf-1 protein which contains the kinase domain. Expression of the lipocortin II-raf cDNA using the murine sarcoma virus long terminal repeat as promoter resulted in the transformation of NIH3T3 cells.
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PMID:A mechanism of c-raf-1 activation: fusion of the lipocortin II amino-terminal sequence with the c-raf-1 kinase domain. 252 24

Results of previous studies have shown that a raf-related transforming DNA sequence is present in NIH 3T3 transformants that are derived from GL-5-JCK human glioblastoma DNA transfection. The transforming DNA was molecularly cloned by using cosmid vector pJB8 to determine its structure and origin. Analyses of selected clones revealed that the transforming DNA consisted of three portions of human DNA sequences, with the 3' half of the c-raf-1 gene as its middle portion. This raf region was about 20 kilobases long and contained exons 8 to 17 and the poly(A) addition site. RNA blot analysis showed that the raf-related transforming DNA was transcribed into 5.3-, 4.8-, and 2.5-kilobase mRNAs; the 2.5-kilobase transcript was thought to be the major transcript. Immunoprecipitation analyses revealed that a 44-kilodalton raf-related protein was specifically expressed in the NIH 3T3 transformants. The raf-related transforming DNA was considered to be activated when its amino-terminal sequence was truncated and the DNA was coupled with a foreign promoter sequence. On hybridization analysis of the original GL-5-JCK glioblastoma DNA, no rearrangement of c-raf-1 was detectable in the tumor DNA. The rearrangement of c-raf-1 may have occurred during transfection or may have been present in a small population of the original tumor cells as a result of tumor progression.
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PMID:Molecular cloning and characterization of an activated human c-raf-1 gene. 329 54