Identification of a family of human F-box proteins
Identification of a family of human F-box proteins
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DOI：
10.1016/s0960-9822(00)80020-2
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发表时间：
1999-10-21
期刊：
影响因子：
9.2
通讯作者：
Pagano, M
中科院分区：
文献类型：
--
作者：
Cenciarelli, C;Chiaur, DS;Pagano, M
F-box蛋白是一个由大约40个氨基酸组成的真核蛋白质家族，其特征是F-box(之所以这样命名是因为细胞周期蛋白F是最早发现这个基序的蛋白质之一)[1]，一些F-box蛋白已被证明对细胞调节蛋白的可控降解至关重要[2，3]。事实上，F-box蛋白是泛素蛋白连接酶的四个亚基之一，称为SCF。另外三个亚基是Skp1蛋白；一种cullin蛋白(在后生动物中为cul1，在酵母中为cdc53或cul A)；以及最近发现的Rod蛋白(也称为Rbx1或Hrt1)，SCF连接酶将泛素结合酶(Ubc3或Ubc4)带到由不同F-box蛋白特异性招募的底物上。酵母和蠕虫对高底物特异性的需要以及已知的大量F-box蛋白[2，4]表明哺乳动物F-box蛋白家族的存在，在酵母双杂交筛选中以Skp1为诱饵，通过搜索DNA数据库，我们鉴定了一个由26个人类F-box蛋白家族组成的家族，其中25个是新的。其中一些蛋白质含有WD-40结构域或富含亮氨酸的重复序列；其他蛋白质要么含有不同的蛋白质相互作用模块，要么没有可识别的基序。我们已经将含有WD-40结构域的F-box蛋白命名为Fbws，那些包含富含亮氨酸重复序列的Fbls，以及其余的Fbxs，我们进一步鉴定了这三类F-box蛋白的代表性成员。
F-box proteins are an expanding family of eukaryotic proteins characterized by an approximately 40 amino-acid motif, the F box (so named because cyclin F was one of the first proteins in which this motif was identified) [1], Some F-box proteins have been shown to be critical for the controlled degradation of cellular regulatory proteins [2,3]. In fact, F-box proteins are one of the four subunits of ubiquitin protein ligases called SCFs. The other three subunits are the Skp1 protein; one of the cullin proteins (Cul1 in metazoans and Cdc53 or Cul A in the yeast Saccharomyces cerevisiae); and the recently identified Rod protein (also called Rbx1 or Hrt1), SCF ligases bring ubiquitin conjugating enzymes (either Ubc3 or Ubc4) to substrates that are specifically recruited by the different F-box proteins. The need for high substrate specificity and the large number of known F box proteins in yeast and worms [2,4] suggest the existence of a large family of mammalian F-box proteins, Using Skp1 as a bait in a yeast two-hybrid screen and by searching DNA databases, we identified a family of 26 human F-box proteins, 25 of which were novel. Some of these proteins contained WD-40 domains or leucine-rich repeats; others contained either different protein-protein interaction modules or no recognizable motifs. We have named the F-box proteins that contain WD-40 domains Fbws, those containing leucine-rich repeats Fbls, and the remaining ones Fbxs, We have further characterized representative members of these three classes of F-box proteins.