Wadman I, Li J, Bash R O, Forster A, Osada H, Rabbitts T H, Baer R
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
EMBO J. 1994 Oct 17;13(20):4831-9. doi: 10.1002/j.1460-2075.1994.tb06809.x.
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.
与T细胞急性淋巴细胞白血病相关的原癌基因的蛋白质产物包括两个不同的假定转录因子家族。RBTN1和RBTN2编码高度相关的蛋白质，这些蛋白质具有富含半胱氨酸的LIM基序。TAL1、TAL2和LYL1编码一个独特的碱性螺旋-环-螺旋（bHLH）蛋白亚组，它们在bHLH序列中具有特殊的同源性。我们发现RBTN1和RBTN2能够与每种致白血病的bHLH蛋白（TAL1、TAL2和LYL1）相互作用。这些相互作用发生在体内，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RBTN1和RBTN2将与TAL1、TAL2和LYL1结合，但不与其他bHLH蛋白结合，包括E12、E47、Id1、NHLH1、AP4、MAX、MYC和MyoD1。此外，RBTN1和RBTN2可以与组装好的bHLH异二聚体中存在的TAL1多肽相互作用（例如TAL1-E47），这表明RBTN蛋白可以影响TAL1的功能特性。最后，我们确定了一部分白血病患者，他们的RBTN2和TAL1基因都存在肿瘤特异性重排。因此，这些基因的激活等位基因可能协同促进白血病，这可能是其蛋白质产物之间bHLH-LIM相互作用的结果。
