SPECIFIC IN-VIVO ASSOCIATION BETWEEN THE BHLH AND LIM PROTEINS IMPLICATED IN HUMAN T-CELL LEUKEMIA
SPECIFIC IN-VIVO ASSOCIATION BETWEEN THE BHLH AND LIM PROTEINS IMPLICATED IN HUMAN T-CELL LEUKEMIA
复制标题
DOI：
10.1002/j.1460-2075.1994.tb06809.x
复制
发表时间：
1994-10-17
期刊：
影响因子：
11.4
通讯作者：
BAER, R
中科院分区：
文献类型：
--
作者：
WADMAN, I;LI, JX;BAER, R
与T细胞急性淋巴细胞白血病有关的原癌基因的蛋白产物包括两个不同的假定转录因子家族，RBTN 1和RBTN 2编码具有富含半胱氨酸的LIM基序的高度相关的蛋白。TAL 1、TAL 2和LYL 1编码碱性螺旋-环-螺旋（bHLH）蛋白的一个独特亚组，它们在它们的bHLH序列中具有异常的同源性。我们已经发现RBTN 1和RBTN 2具有与每种致白血病bHLH蛋白（TAL 1、TAL 2和LYL 1）相互作用的能力。这些相互作用发生在体内，并且似乎是由LIM和bHLH结构域内的序列介导的。LIM-bHLH相互作用具有高度特异性，因为RBTN 1和RBTN 2将与TAL 1、TAL 2和LYL 1结合，但不与其他bHLH蛋白结合，包括E12、E47、Id 1、NHLH 1、AP 4、MAX、MYC和MyoD 1。此外，RBTN 1和RBTN 2可以与存在于组装的bHLH异二聚体（例如TAL 1-E47）中的TAL 1多肽相互作用，表明RBTN蛋白可以影响TAL 1的功能特性。最后，我们已经确定了一个白血病患者的子集，他们的RBTN 2和TAL 1基因都具有肿瘤特异性重排。因此，这些基因的激活等位基因可能协同促进白血病，这可能是它们的蛋白质产物之间的bHLH-LIM相互作用的结果。
The protein products of proto-oncogenes implicated in T cell acute lymphoblastic leukemia include two distinct families of presumptive transcription factors, RBTN1 and RBTN2 encode highly related proteins that possess cysteine-rich LIM motifs. TAL1, TAL2 and LYL1 encode a unique subgroup of basic helix-loop-helix (bHLH) proteins that share exceptional homology in their bHLH sequences. We have found that RBTN1 and RBTN2 have the ability to interact with each of the leukemogenic bHLH proteins (TAL1, TAL2 and LYL1). These interactions occur in vivo and appear to be mediated by sequences within the LIM and bHLH domains. The LIM-bHLH interactions are highly specific in that RBTN1 and RBTN2 will associate with TAL1, TAL2 and LYL1, but not with other bHLH proteins, including E12, E47, Id1, NHLH1, AP4, MAX, MYC and MyoD1. Moreover, RBTN1 and RBTN2 can interact with TAL1 polypeptides that exist in assembled bHLH heterodimers (e.g. TAL1-E47), suggesting that the RBTN proteins can influence the functional properties of TAL1. Finally, we have identified a subset of leukemia patients that harbor tumor-specific rearrangements of both their RBTN2 and TAL1 genes. Thus, the activated alleles of these genes may promote leukemia cooperatively, perhaps as a result of bHLH-LIM interactions between their protein products.