CHARACTERIZATION OF THE VHL TUMOR-SUPPRESSOR GENE-PRODUCT - LOCALIZATION, COMPLEX-FORMATION, AND THE EFFECT OF NATURAL INACTIVATING MUTATIONS
CHARACTERIZATION OF THE VHL TUMOR-SUPPRESSOR GENE-PRODUCT - LOCALIZATION, COMPLEX-FORMATION, AND THE EFFECT OF NATURAL INACTIVATING MUTATIONS
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DOI：
10.1073/pnas.92.14.6459
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发表时间：
1995-07-03
影响因子：
11.1
通讯作者：
KLAUSNER, RD
中科院分区：
文献类型：
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作者：
DUAN, DR;HUMPHREY, JS;KLAUSNER, RD
人类 VHL 肿瘤抑制基因与遗传性疾病 von Hippel-Lindau 病和散发性肾癌有关。同源大鼠基因编码一个 185 个氨基酸的蛋白质，该蛋白质与比对的 213 个氨基酸的人 VHL 基因产物有 88% 的序列相同。当在 COS-7 细胞中表达时，人和大鼠 VHL 蛋白通过免疫荧光显示主要为细胞核、细胞核和细胞质或主要为细胞质 VHL 染色。观察到细胞蛋白的复杂模式可以与引入的 VHL 蛋白特异性共免疫沉淀。观察到的最一致的是含有 VHL 和表观分子质量 16 和 9 kDa 的蛋白质的复合物。某些天然发生的 VHL 错义突变表明 p16-p9 复合物完全或部分丢失。因此，VHL肿瘤抑制基因产物是一种核蛋白，也许能够在细胞核和细胞质之间特异性易位。 VHL 很可能通过形成特定的多蛋白复合物来执行其功能。这些 VHL 相关蛋白的鉴定可能会阐明该肿瘤抑制基因的生理学。
The human VHL tumor suppressor gene has been implicated in the inherited disorder von Hippel-Lindau disease and in sporadic renal carcinoma. The homologous rat gene encodes a 185-amino acid protein that is 88% sequence identical to the aligned 213-amino acid human VHL gene product, When expressed in COS-7 cells, both the human and the rat VHL proteins showed predominant nuclear, nuclear and cytosolic, or predominant cytosolic VHL staining by immunofluorescence. A complicated pattern of cellular proteins was seen that could be specifically coimmunoprecipitated with the introduced VHL protein. A complex containing VHL and proteins of apparent molecular masses 16 and 9 kDa was the most consistently observed. Certain naturally occurring VHL missense mutations demonstrated either complete or partial loss of the p16-p9 complex. Thus, the VHL tumor suppressor gene product is a nuclear protein, perhaps capable of specifically translocating between the nucleus and the cytosol. It is likely that VHL executes its functions via formation of specific multiprotein complexes. Identification of these VHL-associated proteins will likely clarify the physiology of this tumor suppressor gene.