El Hokayem Jimmy, Nawaz Zafar
Department of Biochemistry and Molecular Biology, University of Miami, Miller School of Medicine, 1501 N.W. 10th Avenue, Miami, FL, 33136, USA.
Mol Neurobiol. 2014 Apr;49(2):827-39. doi: 10.1007/s12035-013-8563-y. Epub 2013 Oct 5.
E6-Associated Protein (E6AP), the founding member of the HECT (Homologus to E6AP C terminus) family of ubiquitin ligases, has been gaining increased attention from the scientific community. In addition to its ubiquitin ligase function, our laboratory has also identified steroid hormone receptor transcriptional coactivation as yet another essential function of this protein. Furthermore, it has been established that E6AP has a role in numerous diseases including cancers and neurological syndromes. In this review, we delineate genetic and biochemical knowledge of E6AP and we focus on its role in the pathobiology of neuro-developmental and neuro-aging diseases; bringing to light important gaps of knowledge related to the involvement of its well-studied ligase function versus the much less studied nuclear receptor transcriptional coactivation function in the pathogenesis of these diseases. Tackling these gaps of knowledge could reveal novel possible neuro-pathobiological mechanisms and present crucial information for the design of effective treatment modalities for devastating CNS diseases.
E6相关蛋白（E6AP）是泛素连接酶HECT（与E6AP C末端同源）家族的创始成员，越来越受到科学界的关注。除了其泛素连接酶功能外，我们实验室还确定类固醇激素受体转录共激活是该蛋白的另一项重要功能。此外，已经证实E6AP在包括癌症和神经综合征在内的多种疾病中起作用。在这篇综述中，我们阐述了E6AP的遗传学和生物化学知识，并重点关注其在神经发育和神经衰老疾病病理生物学中的作用；揭示了与其研究充分的连接酶功能相比，其研究较少的核受体转录共激活功能在这些疾病发病机制中的重要知识空白。解决这些知识空白可能揭示新的神经病理生物学机制，并为设计针对毁灭性中枢神经系统疾病的有效治疗方法提供关键信息。
