Identification of a novel human BCL-X promoter and exon.
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.
MacCarthy-Morrogh
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Ludwig Institute for Cancer Research, Imperial College School of Medicine, London, UK.
Wood
L
L
Brimmell
M
M
Johnson
P W
PW
Packham
G
G
D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D022821:RNA Splice Sites; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D018076:DNA, Complementary; D019253:Proto-Oncogene Proteins c-bcl-2; D022821:RNA Splice Sites; D012334:RNA, Neoplasm; D051020:bcl-X Protein