BACKGROUND 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. MAIN BODY OF THE ABSTRACT 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. CONCLUSIONS 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.

中文翻译：

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基于Cullin 2的E3泛素连接酶的结构和调控及其生物学功能。

背景技术Cullin-ring E3泛素连接酶复合物在靶向细胞蛋白以通过26S蛋白酶体进行泛素化依赖性蛋白更新中起着核心作用。Cullin-2是Cullin家族的成员，它充当Elongin B和C，Rbx1和各种底物识别受体的支架蛋白，形成E3泛素连接酶。摘要的主体首先，介绍了基于Cullin-2的E3泛素连接酶的组成，结构和调控。然后描述了以VHL，Lrr-1，Fem1b，Prame，Zyg-11，BAF250，Rack1为底物靶向亚基的复合物的靶标，生物学功能，并讨论了它们在疾病中的参与。介绍了一种作为潜在抗癌药的Cullins小分子抑制剂。此外，描述了可能与Cullin-2结合的带有VHL盒的蛋白质。最后，解释了不同的病毒蛋白如何与Cullin-2形成E3泛素连接酶复合物以对抗宿主病毒防御。结论基于Cullin-2的E3泛素连接酶使用许多不同的底物识别受体，可识别多种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（例如癌症，种系分化和病毒防御）中起关键作用。通过更好地了解它们的生物学特性，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。使用许多不同的底物识别受体，识别多种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（例如癌症，种系分化和病毒防御）中起关键作用。通过更好地了解它们的生物学特性，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。使用许多不同的底物识别受体，识别多种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（例如癌症，种系分化和病毒防御）中起关键作用。通过更好地了解它们的生物学特性，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。