Israel M A, Hernandez M C, Florio M, Andres-Barquin P J, Mantani A, Carter J H, Julin C M
Brain Tumor Research Center, Department of Neurological Surgery, School of Medicine, University of California San Francisco 94143-0520, USA.
Cancer Res. 1999 Apr 1;59(7 Suppl):1726s-1730s.
Id genes encode members of the helix-loop-helix (HLH) family of transcription factors that inhibit transcription by forming inactive heterodimers with basic HLH (bHLH) proteins. There are four members of the Id gene family recognized in mammals, and the proteins they encode share homology primarily in their HLH domain. bHLH proteins typically form heterodimers with other bHLH proteins, and their basic domain binds to a DNA sequence element, the E-box, activating transcription. Products of Id genes lack the basic DNA binding domain of the bHLH transcription factors, and when they heterodimerize with bHLH proteins, the complexes are inactive. Generally, high levels of Id mRNA are detected in proliferative undifferentiated, embryonal cells and lower levels are detected in well-differentiated, mature, adult tissues. In vitro, these genes are generally expressed at lower levels in cells after the induction of differentiation. Recently, high levels of expression of Id genes have been identified in cell lines derived from a wide variety of different tumors and in tumor tissues as well. These findings suggest that not only the inappropriate proliferation of tumors but also the anaplastic characteristics that contribute to their malignant behavior may be regulated by Id gene expression.
Id基因编码转录因子螺旋-环-螺旋（HLH）家族的成员，这些成员通过与碱性HLH（bHLH）蛋白形成无活性的异二聚体来抑制转录。在哺乳动物中已识别出Id基因家族的四个成员，它们编码的蛋白质主要在其HLH结构域具有同源性。bHLH蛋白通常与其他bHLH蛋白形成异二聚体，其碱性结构域与DNA序列元件E盒结合，从而激活转录。Id基因的产物缺乏bHLH转录因子的碱性DNA结合结构域，当它们与bHLH蛋白异二聚化时，形成的复合物无活性。一般来说，在增殖的未分化胚胎细胞中可检测到高水平的Id mRNA，而在分化良好的成熟成年组织中检测到的水平较低。在体外，诱导分化后这些基因在细胞中的表达水平通常较低。最近，在源自多种不同肿瘤的细胞系以及肿瘤组织中也发现了Id基因的高表达。这些发现表明，Id基因的表达不仅可能调节肿瘤的异常增殖，还可能调节导致其恶性行为的间变特征。
