冯·希佩尔-林道肿瘤抑制蛋白对缺氧诱导mRNA的调控需要与包含延伸蛋白B/C和Cul2的复合物结合。
Regulation of hypoxia-inducible mRNAs by the von Hippel-Lindau tumor suppressor protein requires binding to complexes containing elongins B/C and Cul2.
作者信息
Lonergan K M, Iliopoulos O, Ohh M, Kamura T, Conaway R C, Conaway J W, Kaelin W G
机构信息
Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
出版信息
Mol Cell Biol. 1998 Feb;18(2):732-41. doi: 10.1128/MCB.18.2.732.
Abstract
The von Hippel-Lindau tumor suppressor protein (pVHL) binds to elongins B and C and posttranscriptionally regulates the accumulation of hypoxia-inducible mRNAs under normoxic (21% O2) conditions. Here we report that pVHL binds, via elongin C, to the human homolog of the Caenorhabditis elegans Cul2 protein. Coimmunoprecipitation and chromatographic copurification data suggest that pVHL-Cul2 complexes exist in native cells. pVHL mutants that were unable to bind to complexes containing elongin C and Cul2 were likewise unable to inhibit the accumulation of hypoxia-inducible mRNAs. A model for the regulation of hypoxia-inducible mRNAs by pVHL is presented based on the apparent similarity of elongin C and Cul2 to Skp1 and Cdc53, respectively. These latter proteins form complexes that target specific proteins for ubiquitin-dependent proteolysis.
摘要
冯·希佩尔-林道肿瘤抑制蛋白（pVHL）与延伸蛋白B和C结合，并在常氧（21% O₂）条件下对缺氧诱导的mRNA积累进行转录后调控。在此我们报告，pVHL通过延伸蛋白C与秀丽隐杆线虫Cul2蛋白的人类同源物结合。免疫共沉淀和色谱共纯化数据表明，pVHL-Cul2复合物存在于天然细胞中。无法与包含延伸蛋白C和Cul2的复合物结合的pVHL突变体同样无法抑制缺氧诱导的mRNA积累。基于延伸蛋白C和Cul2分别与Skp1和Cdc53的明显相似性，提出了一个pVHL对缺氧诱导的mRNA进行调控的模型。后两种蛋白形成复合物，将特定蛋白靶向进行泛素依赖性蛋白水解。
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