PREFERRED SEQUENCES FOR DNA RECOGNITION BY THE TAL1 HELIX-LOOP-HELIX PROTEINS
PREFERRED SEQUENCES FOR DNA RECOGNITION BY THE TAL1 HELIX-LOOP-HELIX PROTEINS
复制标题
DOI：
10.1128/mcb.14.2.1256
复制
发表时间：
1994-02-01
影响因子：
5.3
通讯作者：
BAER, R
中科院分区：
文献类型：
--
作者：
HSU, HL;HUANG, L;BAER, R
TAL 1基因的肿瘤特异性激活是T细胞急性淋巴细胞白血病患者中最常见的遗传改变。TAL 1基因产物含有碱性螺旋-环-螺旋（bHLH）结构域，这是几种已知转录因子共有的蛋白质二聚体和DNA结合基序。一个结合位点的选择程序，现在已经被用来评估的DNA识别性能的TAL 1。这些研究表明，TAL 1多肽不具有内在的DNA结合活性，大概是因为它们不能形成bHLH同源二聚体。然而，TAL 1容易与任何已知的A类bHLH蛋白（E12、E47、E2-2和HEB）相互作用，形成以序列特异性方式结合DNA的异二聚体。TAL 1异二聚体优先识别可由共有序列AACAGATGGT表示的E-box元件（CANNTG）的子集。该共有序列由参与的A类bHLH多肽（AACAG）和TAL 1多肽（ATGGT）识别的半位点组成。具有DNA结合活性的TAL 1异源二聚体在Jurkat的细胞核提取物中很容易检测到，Jurkat是一种来自T细胞急性淋巴细胞白血病患者的白血病细胞系。因此，TAL 1可能结合并调节独特的次级靶基因子集的转录，其中一些可能介导TAL 1在T细胞白血病发生期间的恶性功能。
Tumor-specific activation of the TAL1 gene is the most common genetic alteration seen in patients with T-cell acute lymphoblastic leukemia. The TAL1 gene products contain the basic helix-loop-helix (bHLH) domain, a protein dimerization and DNA-binding motif common to several known transcription factors. A binding-site selection procedure has now been used to evaluate the DNA recognition properties of TAL1. These studies demonstrate that TAL1 polypeptides do not have intrinsic DNA-binding activity, presumably because of their inability to form bHLH homodimers. However, TAL1 readily interacts with any of the known class A bHLH proteins (E12, E47, E2-2, and HEB) to form heterodimers that bind DNA in a sequence-specific manner. The TAL1 heterodimers preferentially recognize a subset of E-box elements (CANNTG) that can be represented by the consensus sequence AACAGATGGT. This consensus is composed of half-sites for recognition by the participating class A bHLH polypeptide (AACAG) and the TAL1 polypeptide (ATGGT). TAL1 heterodimers with DNA-binding activity are readily detected in nuclear extracts of Jurkat, a leukemic cell line derived from a patient with T-Cell acute lymphoblastic leukemia. Hence, TAL1 is likely to bind a regulate the transcription of unique subset of subordinate target genes, some of which may mediate the malignant function of TAL1 during T-cell leukemogenesis.