Duan D R, Pause A, Burgess W H, Aso T, Chen D Y, Garrett K P, Conaway R C, Conaway J W, Linehan W M, Klausner R D
Urologic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Science. 1995 Sep 8;269(5229):1402-6. doi: 10.1126/science.7660122.
Germline mutations in the von Hippel-Lindau tumor suppressor gene (VHL) predispose individuals to a variety of tumors, including renal carcinoma, hemangioblastoma of the central nervous system, and pheochromocytoma. Here, a cellular transcription factor, Elongin (SIII), is identified as a functional target of the VHL protein. Elongin (SIII) is a heterotrimer consisting of a transcriptionally active subunit (A) and two regulatory subunits (B and C) that activate transcription elongation by RNA polymerase II. The VHL protein was shown to bind tightly and specifically to the Elongin B and C subunits and to inhibit Elongin (SIII) transcriptional activity in vitro. These findings reveal a potentially important transcriptional regulatory network in which the VHL protein may play a key role.
冯·希佩尔-林道肿瘤抑制基因（VHL）的种系突变使个体易患多种肿瘤，包括肾癌、中枢神经系统血管母细胞瘤和嗜铬细胞瘤。在此，一种细胞转录因子延伸蛋白（SIII）被确定为VHL蛋白的功能靶点。延伸蛋白（SIII）是一种异源三聚体，由一个转录活性亚基（A）和两个调节亚基（B和C）组成，它们通过RNA聚合酶II激活转录延伸。VHL蛋白被证明能紧密且特异性地结合延伸蛋白B和C亚基，并在体外抑制延伸蛋白（SIII）的转录活性。这些发现揭示了一个潜在重要的转录调控网络，其中VHL蛋白可能起关键作用。
