Nielsen A L, Norby P L, Pedersen F S, Jorgensen P
Department of Molecular Biology, Aarhus University, C. F. Mollers Allé 130, DK-8000 Aarhus C, Denmark.
J Biol Chem. 1996 Dec 6;271(49):31463-9. doi: 10.1074/jbc.271.49.31463.
TAL1/SCL is a basic helix-loop-helix (bHLH) oncoprotein that is expressed in several cell lines including many hematolymphoid cells, but not in T- and B-lineage cells. The TAL1 gene was originally discovered as being transcriptionally activated by chromosomal rearrangements in T-cell acute lymphoblastic leukemia (T-ALL). Here we have shown that TAL1 and the ubiquitously expressed murine bHLH transcription factor ALF1 formed heterodimers that, compared with ALF1 homodimers, had a more restricted E-box specificity and bound preferentially to the glucocorticoid-responsive E-box (Egre) motif (AACAGATGGT). Overexpression of the dominant inhibitory HLH protein Id1 in NIH3T3 cells reduced the transcriptional activity mediated by ALF1 homodimers, whereas the transcriptional activity mediated by TAL1/ALF1 heterodimers was resistant to Id overexpression. Our results show that ALF1 may serve as a dimerization partner for the bHLH oncoprotein TAL1 and form a complex with a distinctive DNA binding property. These findings support the hypothesis that the leukemic characteristics of the TAL1 oncoprotein could be mediated by activation of a set of target genes as heterodimeric complexes with ubiquitously expressed bHLH transcription factors such as ALF1 and that a principal role of TAL1 might be to neutralize an Id-mediated inactivation.
TAL1/SCL是一种碱性螺旋-环-螺旋（bHLH）癌蛋白，在包括许多血液淋巴细胞在内的多种细胞系中表达，但在T细胞和B细胞系细胞中不表达。TAL1基因最初是在T细胞急性淋巴细胞白血病（T-ALL）中通过染色体重排转录激活而被发现的。在此我们表明，TAL1与普遍表达的小鼠bHLH转录因子ALF1形成异二聚体，与ALF1同二聚体相比，其E盒特异性更受限，且优先结合糖皮质激素反应性E盒（Egre）基序（AACAGATGGT）。在NIH3T3细胞中过表达显性抑制性HLH蛋白Id1可降低由ALF1同二聚体介导的转录活性，而由TAL1/ALF1异二聚体介导的转录活性对Id过表达具有抗性。我们的结果表明，ALF1可能作为bHLH癌蛋白TAL1的二聚化伙伴，并形成具有独特DNA结合特性的复合物。这些发现支持这样一种假说，即TAL1癌蛋白的白血病特征可能是由与普遍表达的bHLH转录因子如ALF1形成异二聚体复合物激活一组靶基因所介导的，并且TAL1的主要作用可能是中和Id介导的失活作用。
