Identification of multiple repeat sequences and transcription-related elements within introns 4, 8 and 9 of human Raf-1.
Oncogenic activation of the human c-raf-1 protein (Raf-1) occurs by truncation of its aminoterminus (regulatory domain) and retention of the carboxyterminus (kinase domain). To gain insight into the structure of human raf-1 genomic DNA corresponding to the regulatory domain of Raf-1, we analyzed the nucleotide sequences of introns 4, 8, and 9. Very high frequencies of the direct and indirect repeats, and A/T nucleotides were observed within introns 4, 8, and 9; and the DNA sequences, 5'-TTAGTCA-3' and 5'-TGATTCA-3', like the DNA recognition site of transcription factor AP-1, were identified within intron 4 of raf-1 in human normal and tumor DNAs. In addition, several transcriptional elements (CAAT box, TATA sequences, eukaryotic transcription initiation sites, and cellular transcriptional elements) were found within introns 4, 8, and 9 of human raf-1. These data suggest: 1) the high frequency of intron-specific repeats is a possible recombinational mechanism for derivation of truncated oncogenic forms of Raf-1; and 2) the multiple transcriptional elements within introns 4, 8, and 9 may have important implications in the regulation of raf-1 transcription and, therefore, its role in cell growth and proliferation.
Jung
M
M
Department of Radiation Medicine, Lombardi Cancer Center, Georgetown University, Washington, D.C. 20007.
Dritschilo
A
A
Mark
G
G
Kasid
U
U
D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry*; D004273:DNA, Neoplasm / Q000737:chemistry; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D010920:Placenta / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D016385:TATA Box; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D004247:DNA; D019908:Proto-Oncogene Proteins c-raf