VHL，抑癌基因的故事。
VHL, the story of a tumour suppressor gene.
机构信息
1] Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Department of Oncology, University of Cambridge, Box 193, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [3] Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
1] Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Department of Oncology, University of Cambridge, Box 193, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
出版信息
Nat Rev Cancer. 2015 Jan;15(1):55-64. doi: 10.1038/nrc3844.
Since the Von Hippel-Lindau (VHL) disease tumour suppressor gene VHL was identified in 1993 as the genetic basis for a rare disorder, it has proved to be of wide medical and scientific interest. VHL tumour suppressor protein (pVHL) plays a key part in cellular oxygen sensing by targeting hypoxia-inducible factors for ubiquitylation and proteasomal degradation. Early inactivation of VHL is commonly seen in clear-cell renal cell carcinoma (ccRCC), and insights gained from the functional analysis of pVHL have provided the foundation for the routine treatment of advanced-stage ccRCC with novel targeted therapies. However, recent sequencing studies have identified additional driver genes that are involved in the pathogenesis of ccRCC. As our understanding of the importance of VHL matures, it is timely to review progress from its initial description to current knowledge of VHL biology, as well as future prospects for novel medical treatments for VHL disease and ccRCC.
自 1993 年发现冯·希佩尔-林道（VHL）疾病肿瘤抑制基因 VHL 是一种罕见疾病的遗传基础以来，它已被证明具有广泛的医学和科学意义。VHL 肿瘤抑制蛋白（pVHL）通过靶向缺氧诱导因子进行泛素化和蛋白酶体降解，在细胞氧感应中发挥关键作用。VHL 的早期失活常见于透明细胞肾细胞癌（ccRCC），对 pVHL 的功能分析的深入了解为新型靶向治疗晚期 ccRCC 提供了基础。然而，最近的测序研究已经确定了其他参与 ccRCC 发病机制的驱动基因。随着我们对 VHL 重要性的认识不断成熟，及时回顾从最初描述到当前 VHL 生物学知识的进展，以及 VHL 疾病和 ccRCC 的新型医学治疗的未来前景是适时的。
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