Biggs J, Murphy E V, Israel M A
Preuss Laboratory for Molecular Neuro-oncology, Department of Neurological Surgery, School of Medicine, University of California, Box 0520, San Francisco 94143.
Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1512-6. doi: 10.1073/pnas.89.4.1512.
The interaction of helix-loop-helix (HLH) proteins is known to regulate the differentiation of several different tissues, including mammalian muscle and the insect peripheral nervous system. In myoblasts, the products of myogenic HLH genes such as MyoD and ubiquitous HLH proteins such as E12 are present at constant levels throughout development. An E12 monomer and a MyoD monomer form a DNA binding heterodimer that activates muscle-specific genes. These two proteins are unable to dimerize in proliferating myoblasts because a negative regulator HLH protein, Id, is present. We now report the sequence and structure of a human HLH gene related to Id, which has been designated Id-2. Two prominent Id-2 RNA molecules of 2.5 and 1.3 kilobases were found in a number of different human normal and neoplastic tissues. We believe the larger RNA is a precursor of the 1.3-kilobase mRNA that encodes an Id-2 protein of 134 amino acids. The HLH region of the Id-2 protein is 90% homologous to that of myogenic Id, but the homology is much less extensive outside the HLH region. The Id-2 gene is highly expressed during early fetal development in several tissues, including those of the central nervous system, but is not expressed in the corresponding mature tissues. Id-2 expression is modulated in association with retinoic acid-induced ganglionic differentiation of the neuroblastoma cell line SMS-KCNR. These findings suggest that Id-2 is an inhibitor of tissue-specific gene expression, although its distinctive pattern of expression during development suggests a role different from that of Id.
已知螺旋-环-螺旋（HLH）蛋白的相互作用可调节多种不同组织的分化，包括哺乳动物肌肉和昆虫外周神经系统。在成肌细胞中，成肌HLH基因（如MyoD）的产物和普遍存在的HLH蛋白（如E12）在整个发育过程中水平恒定。一个E12单体和一个MyoD单体形成一个DNA结合异二聚体，激活肌肉特异性基因。这两种蛋白在增殖的成肌细胞中无法二聚化，因为存在一种负调节HLH蛋白Id。我们现在报告一个与Id相关的人类HLH基因的序列和结构，该基因已被命名为Id-2。在许多不同的人类正常和肿瘤组织中发现了两个主要的2.5和1.3千碱基的Id-2 RNA分子。我们认为较大的RNA是1.3千碱基mRNA的前体，该mRNA编码一个含134个氨基酸的Id-2蛋白。Id-2蛋白的HLH区域与成肌Id的HLH区域有90%的同源性，但在HLH区域之外同源性要小得多。Id-2基因在胎儿早期发育期间在包括中枢神经系统在内的多个组织中高度表达，但在相应的成熟组织中不表达。Id-2的表达与视黄酸诱导的神经母细胞瘤细胞系SMS-KCNR的神经节分化相关。这些发现表明Id-2是组织特异性基因表达的抑制剂，尽管其在发育过程中独特的表达模式表明其作用与Id不同。
