Weiss B, Bollag G, Shannon K
Department of Pediatrics, University of California, San Francisco 94143-0519, USA.
Am J Med Genet. 1999 Mar 26;89(1):14-22.
The NF1 gene encodes neurofibromin, a GTPase-activating protein (GAP) for members of the p21(ras) (Ras) family, which negatively regulates Ras output by accelerating the conversion of active Ras. GTP to inactive Ras.GDP. Analysis of tumors from patients with neurofibromatosis type 1 (NF1) has shown biochemical evidence of hyperactive Ras as well as frequent loss of the normal NF1 allele, consistent with its role as a tumor suppressor gene. Taken together, these data suggest that novel therapeutics directed against components of the Ras signaling cascade might provide effective treatments for certain pathological complications of NF1. Here we summarize data that support a role for hyperactive Ras in NF1 disease, including Ras processing, activation, and down-regulation. We review targets for rational drug design, provide preliminary results, and discuss implications for future studies. Am. J. Med. Genet. (Semin. Med. Genet.) 89:14-22, 1999.
NF1基因编码神经纤维瘤蛋白，它是p21（ras）（Ras）家族成员的一种GTP酶激活蛋白（GAP），通过加速活性Ras·GTP向无活性Ras·GDP的转化来负向调节Ras的输出。对1型神经纤维瘤病（NF1）患者肿瘤的分析已显示出Ras过度活跃的生化证据以及正常NF1等位基因的频繁缺失，这与其作为肿瘤抑制基因的作用一致。综合来看，这些数据表明针对Ras信号级联成分的新型疗法可能为NF1的某些病理并发症提供有效治疗。在此，我们总结支持Ras过度活跃在NF1疾病中作用的数据，包括Ras的加工、激活和下调。我们回顾合理药物设计的靶点，提供初步结果，并讨论对未来研究的意义。《美国医学遗传学杂志》（医学遗传学研讨会）89:14 - 22，1999年。
