MacCarthy-Morrogh L, Wood L, Brimmell M, Johnson P W, Packham G
Ludwig Institute for Cancer Research, Imperial College School of Medicine, London, UK.
Oncogene. 2000 Nov 16;19(48):5534-8. doi: 10.1038/sj.onc.1203949.
BCL-XL is a key anti-apoptotic BCL-2 family protein that is widely expressed in human cancer cells and is induced in response to diverse survival signals. The translation initiation codon for BCL-XL is located in BCL-X exon II and previous analyses have indicated that BCL-XL RNAs initiate close to the start of exon II or additionally contain a non-coding first exon (exon IA) spliced to exon II. Using 5' RACE we have now identified a novel BCL-X non-coding exon (exon IB) which is spliced directly to exon II in place of exon IA. Exon IB-containing RNAs encoded BCL-XL and were detected in non-malignant lymphocytes and lymphoma cells from lymph node biopsies and were expressed at significant levels in cell lines derived from ovarian, colon and breast cancers. We identified two TATA-box sequences upstream of exon IB and demonstrated that surrounding genomic sequences contained strong promoter activity in lymphoma cells (approximately 300-fold active relative to controls). We have therefore identified a powerful new BCL-X promoter and a novel exon that contributes to BCL-XL expression.
BCL-XL是一种关键的抗凋亡BCL-2家族蛋白，在人类癌细胞中广泛表达，并在多种生存信号的作用下被诱导表达。BCL-XL的翻译起始密码子位于BCL-X外显子II中，先前的分析表明，BCL-XL RNA在靠近外显子II起始处开始转录，或者额外包含一个剪接到外显子II的非编码第一外显子（外显子IA）。利用5' RACE技术，我们现在鉴定出一个新的BCL-X非编码外显子（外显子IB），它直接剪接到外显子II，取代了外显子IA。含外显子IB的RNA编码BCL-XL，在非恶性淋巴细胞以及淋巴结活检的淋巴瘤细胞中被检测到，并在源自卵巢癌、结肠癌和乳腺癌的细胞系中大量表达。我们在位于外显子IB上游鉴定出两个TATA框序列，并证明周围的基因组序列在淋巴瘤细胞中具有很强的启动子活性（相对于对照约有300倍的活性）。因此，我们鉴定出一个强大的新的BCL-X启动子和一个对BCL-XL表达有贡献的新外显子。
