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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G and Thompson CB. . 1993 Cell 74: 597–608.
Choi MS, Boise LH, Gottschalk AR, Quintans J, Thompson CB and Klaus GG. . 1995 Eur. J. Immunol. 25: 1352–1357.
Datta R, Manome Y, Taneja N, Boise LH, Weichselbaum R, Thompson CB, Slapak CA and Kufe D. . 1995 Cell Growth Differ. 4: 363–370.
Fang W, Rivard JJ, Mueller DL and Behrens TW. . 1994 J. Immunol. 153: 4388–4399.
Gonzalez-Garcia M, Perez Ballestero R, Ding L, Duan L, Boise LH, Thompson CB and Nunez G. . 1994 Development 120: 3033–3042.
Gotteschalk AR, Boise LH, Thompson CB and Quintans J. . 1994 Proc. Natl. Acad. Sci. USA 91: 7350–7354.
Grillot DA, Gonzalez-Garcia M, Ekhterae D, Duan L, Inohara N, Ohta S, Seldin MF and Nunez G. . 1997 J. Immunol. 158: 4750–4757.
Grillot DA, Merino R and Nunez G. . 1995 J. Exp. Med. 182: 1973–1983.
Harigai M, Miyashita T, Hanada M and Reed JC. . 1996 Oncogene 12: 1369–1374.
Krajewska M, Moss SF, Krajewski S, Song K, Holt PR and Reed JC. . 1996 Cancer Res. 56: 2422–2427.
Lohmann CM, League AA, Clark WS, Lawson D, DeRose PB and Cohen C. . 2000 Cytometry 42: 61–66.
Minn AJ, Rudin CM, Boise LH and Thompson CB. . 1995 Blood 86: 1903–1910.
Naik P, Karrim J and Hanahan D. . 1996 Genes Dev. 10: 2105–2116.
Olopade OI, Adeyanju MO, Safa AR, Hagos F, Mick R, Thompson CB and Recant WM. . 1997 Cancer J. Sci. Am. 3: 230–237.
Packham G, White EL, Eischen CM, Yang H, Parganas E, Ihle JN, Grillot DAM, Zambetti GP, Nunez G and Cleveland JL. . 1998 Genes Dev. 12: 2475–2487.
Pena JC, Rudin CM and Thompson CB. . 1998 Cancer Res. 58: 2111–2116.
Rodeck U, Jost M, DuHadaway J, Kari C, Jensen PJ, Risse B and Ewert DL. . 1997 Proc. Natl. Acad. Sci. USA 94: 5067–5072.
Schott AF, Apel IJ, Nunez G and Clarke MF. . 1995 Oncogene 11: 1389–1394.
Xerri L, Parc P, Brousset P, Schlaifer D, Hassoun J, Reed JC, Krajewski S and Birnbaum D. . 1996 Br. J. Haematol. 92: 900–906.
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.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1203949
Keywords
This article is cited by
-
The BAG-1 cochaperone is a negative regulator of p73-dependent transcription
British Journal of Cancer (2009)
-
Distinct promoters mediate constitutive and inducible Bcl-XL expression in malignant lymphocytes
Oncogene (2007)
-
Upregulation of BAK by butyrate in the colon is associated with increased Sp3 binding
Oncogene (2006)