Department of Microbiology, Immunology and Genetics, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, United States.
Department of Microbiology, Immunology and Genetics, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, United States.
Virus Res. 2023 Oct 2;335:199191. doi: 10.1016/j.virusres.2023.199191. Epub 2023 Aug 4.
The Ubiquitin-protein ligase E3A, UBE3A, also known as E6-associated protein (E6-AP), is known to play an essential role in regulating the degradation of various proteins by transferring Ub from E2 Ub conjugating enzymes to the substrate proteins. Several studies indicate that UBE3A regulates the stabilities of key viral proteins in the virus-infected cells and, thereby, the infected virus-mediated diseases, even if it were reported that UBE3A participates in non-viral-related human diseases. Furthermore, mutations such as deletions and duplications in the maternally inherited gene in the brain cause human neurodevelopmental disorders such as Angelman syndrome (AS) and autism. It is also known that UBE3A functions as a transcriptional coactivator for the expression of steroid hormone receptors. These reports establish that UBE3A is distinguished by its multitudinous functions that are paramount to viral pathology and human diseases. This review is focused on molecular mechanisms for such intensive participation of UBE3A in disease formation and virus regulation.
泛素蛋白连接酶 E3A（UBE3A），也称为 E6 相关蛋白（E6-AP），已知在通过将 Ub 从 E2 Ub 连接酶转移到底物蛋白上来调节各种蛋白质的降解中发挥重要作用。几项研究表明，UBE3A 调节病毒感染细胞中关键病毒蛋白的稳定性，从而调节感染病毒介导的疾病，即使有报道称 UBE3A 参与非病毒相关的人类疾病。此外，在大脑中母系遗传基因中的缺失和重复突变会导致人类神经发育障碍，如 Angelman 综合征（AS）和自闭症。还已知 UBE3A 作为甾体激素受体表达的转录共激活因子发挥作用。这些报告表明，UBE3A 因其对病毒病理学和人类疾病的多种功能而与众不同。这篇综述重点介绍了 UBE3A 如此强烈参与疾病形成和病毒调节的分子机制。
