Identification of multiple repeat sequences and transcription-related elements within introns 4, 8 and 9 of human Raf-1.
Identification of multiple repeat sequences and transcription-related elements within introns 4, 8 and 9 of human Raf-1.
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鉴定人 Raf-1 内含子 4、8 和 9 内的多个重复序列和转录相关元件。
DOI：
10.1006/bbrc.1993.1070
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发表时间：
1993
影响因子：
3.1
通讯作者：
Kasid,U
中科院分区：
文献类型：
--
作者：
Jung,M;Dritschilo,A;Mark,G;Kasid,U
人c-raf-1蛋白（Raf-l）的致癌激活通过其氨基末端（调节结构域）的截短和羧基末端（激酶结构域）的保留而发生。为了深入了解与Raf-1调控结构域对应的humanraf-1基因组DNA的结构，我们分析了内含子4、8和9的核苷酸序列。在人类正常和肿瘤DNA中，在内含子4、8和9中发现了很高频率的直接和间接重复序列以及A/T核苷酸，并在内含子4中发现了与转录因子AP-1的DNA识别位点相似的DNA序列5′-TTAGTCA-3′和5′-TGATTCA-3′。此外，几个转录元件（CAAT盒，TATA序列，真核生物转录起始位点，和细胞转录元件）内发现humanraf-1的内含子4，8和9。这些数据表明：1）内含子特异性重复的高频率是Raf-1的截短致癌形式的衍生的可能的重组机制; 2）内含子4、8和9内的多个转录元件可能在Raf-1转录的调节中具有重要意义，因此，其在细胞生长和增殖中的作用。
Oncogenic activation of the human c-raf-1 protein (Raf-l) occurs by truncation of its aminoterminus (regulatory domain) and retention of the carboxyterminus (kinase domain). To gain insight into the structure of humanraf-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 ofraf-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 humanraf-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 ofraf-1 transcription and, therefore, its role in cell growth and proliferation.