Xia Y, Hwang L Y, Cobb M H, Baer R
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Oncogene. 1994 May;9(5):1437-46.
The TAL2 gene is activated as a result of the (7;9) (q34;q32) translocation, a chromosome defect found in the malignant cells of some patients with T-cell acute lymphoblastic leukemia (T-ALL). TAL2 potentially encodes a basic helix-loop-helix motif that is highly related to those specified by TAL1 and LYL1, distinct genes that have also been implicated in T-ALL. In this report we show that leukemic cells bearing the (7;9) (q34;q32) translocation express a TAL2 gene product of 108 amino acids. In leukemic cells this product exists in both a phosphorylated (pp13TAL2) and an unphosphorylated (p12TAL2) form. Serine residue 100 is the major site of TAL2 phosphorylation in vivo, and it serves as an effective in vitro substrate for mitogen-activated protein (MAP) kinases such as ERK1. TAL2 polypeptides interact in vivo with the E2A gene products (E47 and E12) to form bHLH heterodimers that bind DNA in a sequence-specific manner. The TAL2 polypeptides do not bind DNA by themselves, however, suggesting that their functional properties may be contingent upon association with other bHLH proteins. Taken together, the properties of TAL2 evaluated here broadly resemble those described previously for TAL1, and therefore support the idea that both proteins promote T-ALL by a common mechanism.
TAL2基因因（7；9）（q34；q32）易位而被激活，这是在一些T细胞急性淋巴细胞白血病（T-ALL）患者的恶性细胞中发现的一种染色体缺陷。TAL2可能编码一种碱性螺旋-环-螺旋基序，该基序与TAL1和LYL1所特有的基序高度相关，TAL1和LYL1是另外两个也与T-ALL有关的不同基因。在本报告中，我们显示携带（7；9）（q34；q32）易位的白血病细胞表达一种由108个氨基酸组成的TAL2基因产物。在白血病细胞中，该产物以磷酸化（pp13TAL2）和未磷酸化（p12TAL2）两种形式存在。丝氨酸残基100是TAL2在体内磷酸化的主要位点，并且它是丝裂原活化蛋白（MAP）激酶（如ERK1）有效的体外底物。TAL2多肽在体内与E2A基因产物（E47和E12）相互作用，形成以序列特异性方式结合DNA的bHLH异二聚体。然而，TAL2多肽自身并不结合DNA，这表明它们的功能特性可能取决于与其他bHLH蛋白的结合。综上所述，本文评估的TAL2的特性与先前描述的TAL1的特性大致相似，因此支持这两种蛋白通过共同机制促进T-ALL的观点。
