Transcriptional activity of TAL1 in T cell acute lymphoblastic leukemia (T-ALL) requires RBTN1 or -2 and induces TALLA1, a highly specific tumor marker of T-ALL

被引:45
作者
Ono, Y [1 ]
Fukuhara, N [1 ]
Yoshie, O [1 ]
机构
[1] SHIONOGI INST MED SCI,SETTSU,OSAKA 566,JAPAN
关键词
D O I
10.1074/jbc.272.7.4576
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
TAL1, which is frequently activated in T cell acute lymphoblastic leukemia (T-ALL), encodes lineage-specific basic helix-loop-helix (bHLH) proteins that bind specifically to E-box DNA motif upon dimerization with ubiquitous basic helix-loop-helix proteins E47 or E12, RBTN1 and RBTN2, also frequently activated in T-ALL, encode proteins only with tandem cysteine-rich LIM domains, We found that aberrant expression of TAL1 detected in 11 out of 14 T-ALL cell lines was invariably accompanied by that of either RBTN1 or RBTN2, Forced expression of TAL1 together with RBTN1 or RBTN2, but not TAL1 alone, strongly induced artificial reporter genes in a TAL1/RBTN-negative T-ALL cell Line, HPB-ALL, Such collaborative transcriptional activity of TAL1 and RBTN was not, however, observed in non-T cell lines, suggesting further involvement of some T cell-specific cofactors. In this context, we carried out preliminary evaluation of a potential role of the T cell-specific GATA-binding protein, GATA3, in the transcriptional activity of TAL1 and RBTN. We also showed that coexpression of TAL1 and RBTN1 in HPB-ALL strongly induced TALLA1, a highly specific T-ALL marker whose positivity correlated 100% with ectopic expression of TAL1 among various T-ALL cell lines, Collectively, ectopic TAL1 and RBTN1 or -2, together with some endogenous T cell-specific cofactors like GATA3, constitute a highly collaborative set of transcription factors whose aberrant activity in T cells may lead to leukemogenesis by modulating expression of downstream genes such as TALLA1.
引用
收藏
页码:4576 / 4581
页数:6
相关论文
共 40 条
[1]   THE SCL GENE-PRODUCT - A POSITIVE REGULATOR OF ERYTHROID-DIFFERENTIATION [J].
APLAN, PD ;
NAKAHARA, K ;
ORKIN, SH ;
KIRSCH, IR .
EMBO JOURNAL, 1992, 11 (11) :4073-4081
[2]  
BAER R, 1993, SEMIN CANCER BIOL, V4, P341
[3]   DOES ACTIVATION OF THE TAL1 GENE OCCUR IN A MAJORITY OF PATIENTS WITH T-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA - A PEDIATRIC-ONCOLOGY-GROUP STUDY [J].
BASH, RO ;
HALL, S ;
TIMMONS, CF ;
CRIST, WM ;
AMYLON, M ;
SMITH, RG ;
BAER, R .
BLOOD, 1995, 86 (02) :666-676
[4]  
BERNARD O, 1991, ONCOGENE, V6, P1477
[5]   THE RHOMBOTIN FAMILY OF CYSTEINE-RICH LIM-DOMAIN ONCOGENES - DISTINCT MEMBERS ARE INVOLVED IN T-CELL TRANSLOCATIONS TO HUMAN CHROMOSOME-11P15 AND CHROMOSOME-11P13 [J].
BOEHM, T ;
FORONI, L ;
KANEKO, Y ;
PERUTZ, MF ;
RABBITTS, TH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (10) :4367-4371
[6]  
ELWOOD NJ, 1995, CELL GROWTH DIFFER, V6, P19
[7]  
ELWOOD NJ, 1993, ONCOGENE, V8, P3093
[8]  
FISCH P, 1992, ONCOGENE, V7, P2389
[9]   THE RHOMBOTIN GENE FAMILY ENCODE RELATED LIM-DOMAIN PROTEINS WHOSE DIFFERING EXPRESSION SUGGESTS MULTIPLE ROLES IN MOUSE DEVELOPMENT [J].
FORONI, L ;
BOEHM, T ;
WHITE, L ;
FORSTER, A ;
SHERRINGTON, P ;
LIAO, XB ;
BRANNAN, CI ;
JENKINS, NA ;
COPELAND, NG ;
RABBITTS, TH .
JOURNAL OF MOLECULAR BIOLOGY, 1992, 226 (03) :747-761
[10]   HUMAN GATA-3 - A LINEAGE-RESTRICTED TRANSCRIPTION FACTOR THAT REGULATES THE EXPRESSION OF THE T-CELL RECEPTOR ALPHA-GENE [J].
HO, IC ;
VORHEES, P ;
MARIN, N ;
OAKLEY, BK ;
TSAI, SF ;
ORKIN, SH ;
LEIDEN, JM .
EMBO JOURNAL, 1991, 10 (05) :1187-1192