Identification of a novel human BCL-X promoter and exon

被引:14
作者
MacCarthy-Morrogh, L
Wood, L
Brimmell, M
Johnson, PWM
Packham, G
机构
[1] Univ Southampton, Southampton Gen Hosp, Sch Med, CRC Wessex Med Oncol Unit,Canc Sci Div, Southampton SO16 6YD, Hants, England
[2] Univ London Imperial Coll Sci Technol & Med, Ludwig Inst Canc Res, Sch Med, London W12 1PG, England
关键词
apoptosis; BCL-X-L; splicing; promoter; transcription;
D O I
10.1038/sj.onc.1203949
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
BCL-X-L 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-X-L is located in BCL-X exon II and previous analyses have indicated that BCL-X-L RNAs initiate close to the start of exon IT or additionally contain a non-coding first exon (exon IA) spliced to exon TI, Using 5' RACE we have now identified a novel BCL-X non-coding exon (exon IB) which is spliced directly to exon IJ[ in place of exon IA, Exon IB-containing RNAs encoded BCL-X-L and were detected in non-malignant lymphocytes and lymphoma cells from lymph node biopsies and mere expressed at significant levels in cell lines derived from ovarian, colon and breast cancers. We identified two TATA-hox sequences upstream of exon TB 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-X-L expression.
引用
收藏
页码:5534 / 5538
页数:5
相关论文
共 20 条
[1]   BCL-X, A BCL-2-RELATED GENE THAT FUNCTIONS AS A DOMINANT REGULATOR OF APOPTOTIC CELL-DEATH [J].
BOISE, LH ;
GONZALEZGARCIA, M ;
POSTEMA, CE ;
DING, LY ;
LINDSTEN, T ;
TURKA, LA ;
MAO, XH ;
NUNEZ, G ;
THOMPSON, CB .
CELL, 1993, 74 (04) :597-608
[2]   THE ROLE OF BCL-X(L) IN CD40-MEDIATED RESCUE FROM ANTI-MU-INDUCED APOPTOSIS IN WEHI-231 B-LYMPHOMA-CELLS [J].
CHOI, MSK ;
BOISE, LH ;
GOTTSCHALK, AR ;
QUINTANS, J ;
THOMPSON, CB ;
KLAUS, GGB .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (05) :1352-1357
[3]  
DATTA R, 1995, CELL GROWTH DIFFER, V6, P363
[4]  
FANG W, 1994, J IMMUNOL, V153, P4388
[5]  
GONZALEZGARCIA M, 1994, DEVELOPMENT, V120, P3033
[6]   IDENTIFICATION OF IMMUNOSUPPRESSANT-INDUCED APOPTOSIS IN A MURINE B-CELL LINE AND ITS PREVENTION BY BCL-X BUT NOT BCL-2 [J].
GOTTSCHALK, AR ;
BOISE, LH ;
THOMPSON, CB ;
QUINTANS, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (15) :7350-7354
[7]   BCL-X(L) DISPLAYS RESTRICTED DISTRIBUTION DURING T-CELL DEVELOPMENT AND INHIBITS MULTIPLE FORMS OF APOPTOSIS BUT NOT CLONAL DELETION IN TRANSGENIC MICE [J].
GRILLOT, DAM ;
MERINO, R ;
NUNEZ, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (06) :1973-1983
[8]  
Grillot DAM, 1997, J IMMUNOL, V158, P4750
[9]  
Harigai M, 1996, ONCOGENE, V12, P1369
[10]  
Krajewska M, 1996, CANCER RES, V56, P2422