von Hippel-Lindau tumor suppressor: not only HIF's executioner
von Hippel-Lindau tumor suppressor: not only HIF's executioner
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DOI：
10.1016/j.molmed.2004.02.004
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发表时间：
2004-04-01
影响因子：
13.6
通讯作者：
Meller, J
中科院分区：
文献类型：
--
作者：
Czyzyk-Krzeska, MF;Meller, J
von Hippel-Lindau (VHL) 蛋白功能丧失会导致常染色体显性癌症综合征，称为 VHL 疾病，表现为视网膜血管瘤、中枢神经系统血管母细胞瘤、肾透明细胞癌和嗜铬细胞瘤。 VHL 肿瘤抑制因子是 E3 泛素复合物的特异性底物识别成分，可调节 a 的蛋白酶体降解。缺氧诱导转录因子 (HIF) 的亚基。 VHL 复合体功能受损会导致 HIF 积累、各种 HIF 诱导的基因产物过度表达以及高度血管瘤的形成。然而，VHL 复合物的泛素化作用超出了其调节 HIF 的功能，因为它似乎调节可能参与致癌过程各个步骤的其他蛋白质的稳定性。
Loss of von Hippel-Lindau (VHL) protein function results in an autosomal-dominant cancer syndrome known as VHL disease, which manifests as angiomas of the retina, hemangioblastomas of the central nervous system, renal clear-cell carcinomas and pheochromocytomas. VHL tumor suppressor is a specific substrate-recognition component of the E3 ubiquitin complex, which regulates proteasomal degradation of the a. subunit of the hypoxia inducible transcription factor (HIF). Impaired VHL complex function leads to accumulation of HIF, overexpression of various HIF-induced gene products and formation of highly vascular neoplasia. However, the ubiquitylating role of the VHL complex extends beyond its function in regulating HIF, as it appears to regulate the stability of other proteins that might be involved in various steps of oncogenic processes.