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Identification of a novel human BCL-X promoter and exon

Abstract

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.

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Acknowledgements

We would like to thank Dr Bridgit Wilkins and Jo-Anne Gregory for providing and preparation of primary lymph nodes. This work was supported by the Ludwig Institute for Cancer Research and the Cancer Research Campaign.

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MacCarthy-Morrogh, L., Wood, L., Brimmell, M. et al. Identification of a novel human BCL-X promoter and exon. Oncogene 19, 5534–5538 (2000). https://doi.org/10.1038/sj.onc.1203949

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