Gankyrin, the 26 S proteasome, the cell cycle and cancer
Gankyrin, the 26 S proteasome, the cell cycle and cancer
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DOI：
10.1042/bst0340746
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发表时间：
2006-11-01
影响因子：
3.9
通讯作者：
Fujita, J.
中科院分区：
文献类型：
--
作者：
Mayer, R. J.;Fujita, J.
细胞周期调控中已知的分子参与者被大量研究，不仅是为了了解更多关于这个复杂系统的信息，也是为了了解致癌转化的分子特征。很少会发现改变细胞周期控制解释的新参与者。Gankyrin就是这样的参与者之一，在酵母双杂交筛选中被发现是一种新的蛋白酶体亚基，它与S6 b（rpt 3）AAA（与各种细胞活动相关的ATP酶）ATP酶特异性相互作用，该ATP酶与其他五种AAA一起存在于所谓的26 S蛋白酶体19 S调节子的碱基中。Gankyrin也是第一个肝脏癌基因。Gankyrin存在于其他含有Rb（视网膜母细胞瘤蛋白）和泛素蛋白连接酶Mdm 2（鼠双微体2）的复合物中。Gankyrin增加Rb的过度磷酸化，因此激活DNA合成基因的E2F依赖性转录。此外，Gankyrin通过与Mdm 2结合，增加了p53的泛素化和降解，并防止细胞凋亡。Gankyrin控制两个主要肿瘤抑制因子的功能，并且当过度表达时，导致肝细胞癌。
The known molecular players in cell-cycle control are much studied, not only to learn more about this intricate system, but also to understand the molecular features of oncogenic transformation. Infrequently, new players are discovered that change the interpretation of cell-cycle control. Gankyrin is one such player and was discovered in yeast two-hybrid screens as a new proteasomal subunit that interacts specifically with the S6b (rpt3) AAA (ATPase associated with various cellular activities) ATPase, which, with five other AAAs, are present in the so-called base of the 19 S regulator of the 26 S proteasome. Gankyrin is also the first liver oncogene. Gankyrin is found in other complexes that contain Rb (retinoblastoma protein) and the ubiquitin protein ligase Mdm2 (murine double minute 2). Gankyrin increases the hyperphosphorylation of Rb and therefore activates E2F-dependent transcription of DNA synthesis genes. Additionally, gankyrin, by binding to Mdm2, increases the ubiquitylation and degradation of p53 and prevents apoptosis. Gankyrin controls the functions of two major tumour suppressors and, when overexpressed, causes hepatocellular carcinoma.