The structure and regulation of Cullin 2 based E3 ubiquitin ligases and their biological functions.
The structure and regulation of Cullin 2 based E3 ubiquitin ligases and their biological functions.
复制标题
基于Cullin 2的E3泛素连接酶及其生物学功能的结构和调节。
DOI：
10.1186/s13008-016-0020-7
复制
发表时间：
2016
期刊：
影响因子：
2.3
通讯作者：
Yang H
中科院分区：
文献类型：
--
作者：
Cai W;Yang H
Cullin-RING E3泛素连接酶复合物在靶向细胞蛋白以通过26 S蛋白酶体进行泛素化依赖的蛋白质周转中发挥核心作用。Cullin-2是Cullin家族的成员，它作为延伸蛋白B和C、Rbx 1和各种底物识别受体的支架蛋白，形成E3泛素连接酶。首先介绍了Cullin-2泛素连接酶的组成、结构和调控。然后介绍了以VHL、Lrr-1、Fem 1b、Prame、Zyg-11、BAF 250、Rack 1等为底物靶向亚基的复合物的靶点、生物学功能及其与疾病的关系。介绍了一种具有潜在抗癌潜力的Cullins小分子抑制剂。此外，还发现了可能与Cullin-2结合的VHL盒蛋白。最后，解释了不同的病毒蛋白如何与Cullin-2形成E3泛素连接酶复合物来对抗宿主病毒防御。基于Cullin-2的E3泛素连接酶使用许多不同的底物识别受体，识别许多底物并调节其蛋白质稳定性。这些复合物在生物过程和疾病如癌症、生殖细胞分化和病毒防御中起着关键作用。通过更好地了解它们的生物学，我们可以设计和开发新的治疗策略来治疗癌症，遗传性疾病和病毒感染。
Cullin-RING E3 ubiquitin ligase complexes play a central role in targeting cellular proteins for ubiquitination-dependent protein turnover through 26S proteasome. Cullin-2 is a member of the Cullin family, and it serves as a scaffold protein for Elongin B and C, Rbx1 and various substrate recognition receptors to form E3 ubiquitin ligases. First, the composition, structure and the regulation of Cullin-2 based E3 ubiquitin ligases were introduced. Then the targets, the biological functions of complexes that use VHL, Lrr-1, Fem1b, Prame, Zyg-11, BAF250, Rack1 as substrate targeting subunits were described, and their involvement in diseases was discussed. A small molecule inhibitor of Cullins as a potential anti-cancer drug was introduced. Furthermore, proteins with VHL box that might bind to Cullin-2 were described. Finally, how different viral proteins form E3 ubiquitin ligase complexes with Cullin-2 to counter host viral defense were explained. Cullin-2 based E3 ubiquitin ligases, using many different substrate recognition receptors, recognize a number of substrates and regulate their protein stability. These complexes play critical roles in biological processes and diseases such as cancer, germline differentiation and viral defense. Through the better understanding of their biology, we can devise and develop new therapeutic strategies to treat cancers, inherited diseases and viral infections.