Cenciarelli C, Chiaur D S, Guardavaccaro D, Parks W, Vidal M, Pagano M
Department of Pathology, Kaplan Comprehensive Cancer Center, MSB 548, New York University School of Medicine 550 First Avenue, New York, New York, 10016, USA.
Curr Biol. 1999 Oct 21;9(20):1177-9. doi: 10.1016/S0960-9822(00)80020-2.
F-box proteins are an expanding family of eukaryotic proteins characterized by an approximately 40 aminoacid 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 Roc1 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.
F-box蛋白是真核生物蛋白中不断扩展的一个家族，其特征是具有一个约40个氨基酸的基序，即F盒（之所以这样命名，是因为细胞周期蛋白F是最早发现该基序的蛋白之一）[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]。实际上，F-box蛋白是称为SCF的泛素蛋白连接酶的四个亚基之一。另外三个亚基是Skp1蛋白；一种cullin蛋白（后生动物中的Cul1以及酿酒酵母中的Cdc53或Cul A）；以及最近鉴定出的Roc1蛋白（也称为Rbx1或Hrt1）。SCF连接酶将泛素缀合酶（Ubc3或Ubc4）带到由不同F-box蛋白特异性招募的底物上。酵母和蠕虫中对高底物特异性的需求以及大量已知的F-box蛋白[2][4]表明存在一个庞大的哺乳动物F-box蛋白家族。我们在酵母双杂交筛选中以Skp1为诱饵，并通过搜索DNA数据库，鉴定出一个由26种人类F-box蛋白组成的家族，其中25种是新发现的。这些蛋白中的一些含有WD-40结构域或富含亮氨酸的重复序列；其他蛋白则含有不同的蛋白质-蛋白质相互作用模块或没有可识别的基序。我们将含有WD-40结构域的F-box蛋白命名为Fbws，含有富含亮氨酸重复序列的命名为Fbls，其余的命名为Fbxs。我们进一步对这三类F-box蛋白的代表性成员进行了表征。
