FORMATION OF IN-VIVO COMPLEXES BETWEEN THE TAL1 AND E2A POLYPEPTIDES OF LEUKEMIC T-CELLS
FORMATION OF IN-VIVO COMPLEXES BETWEEN THE TAL1 AND E2A POLYPEPTIDES OF LEUKEMIC T-CELLS
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DOI：
10.1073/pnas.91.8.3181
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发表时间：
1994-04-12
影响因子：
11.1
通讯作者：
BAER, R
中科院分区：
文献类型：
--
作者：
HSU, HL;WADMAN, I;BAER, R
TAL 1基因的肿瘤特异性激活发生在几乎等于25%的T细胞急性淋巴细胞白血病（T-ALL）患者中。TAL 1基因产物具有碱性螺旋-环-螺旋（bHLH）结构域，其在体外与由E2 A基因座编码的bHLH蛋白（E12和E47）相互作用。我们现在已经应用了两种独立的方法，双杂交程序和免疫共沉淀分析，以证明TAL 1和E2 A多肽也在体内关联。这些研究表明TAL 1的bHLH结构域选择性地与E12和E47的bHLH结构域相互作用，但不与Id 1螺旋-环-螺旋蛋白相互作用。TAL 1不自缔合形成同源二聚体复合物，这意味着TAL 1的体内功能取决于与其他bHLH蛋白如E12和E47的异源相互作用。免疫共沉淀分析揭示了Jurkat细胞中内源性TAL 1/E2 A复合物的存在，Jurkat细胞是一种来自T-ALL患者的白血病细胞系。因此，TAL 1的恶性性质可能是由于与E2 A多肽的专性相互作用。
Tumor-specific activation of the TAL1 gene occurs in almost-equal-to 25% of patients with T-cell acute lymphoblastic leukemia (T-ALL). The TAL1 gene products possess a basic helix-loop-helix (bHLH) domain that interacts in vitro with the bHLH proteins (E12 and E47) encoded by the E2A locus. We have now applied two independent methods, the two-hybrid procedure and co-immunoprecipitation analysis, to demonstrate that TAL1 and E2A polypeptides also associate in vivo. These studies show that the bHLH domain of TAL1 selectively interacts with the bHLH domains of E12 and E47, but not with the Id1 helix-loop-helix protein. TAL1 does not self-associate to form homodimeric complexes, implying that the in vivo functions of TAL1 depend on heterologous interaction with other bHLH proteins such as E12 and E47. Co-immunoprecipitation analysis revealed the presence of endogenous TAL1/E2A complexes in Jurkat cells, a leukemic line derived from a T-ALL patient. Thus, the malignant properties of TAL1 may be due to obligate interaction with the E2A polypeptides.