泛素化能够促使底物蛋白降解或调节其它生理过程,在生命活动中具有极其重要的作用。E3即泛素连接酶,在泛素化过程中决定底物分子的特异性,因此,E3的功能研究一直是蛋白质泛素化研究领域的一个热点。NEDLl和NEDL2是HECT类泛素连接酶NEDD4家族中同源性较高的两个成员。它们通过不同的方式分别增强p53和p73的转录活性。NEDLl又与多种肿瘤(如神经母细胞瘤、结直肠癌、乳腺癌)和神经退行性疾病(如脊髓侧索硬化病)的发生发展密切相关。因此,对NEDLl和NEDL2的研究对于揭示相关疾病机理具有非常重要的意义.
Ubiquitination plays a critical role in life by regulating protein degradation as well as a wide array of cellular activities. The E3 enzymes dictate the specificity of ubiquitylation, and is presently an area of intense research and extensive scientific interest. NEDL1 and NEDL2 are all the members of the NEDD4 family that belong to the HECT enzymes. NEDL1 has an ability to enhance the transcriptional activity of p53 to induce apoptosis. However, NEDL2 specifically enhanced the p73-dependent transcriptional activation by increasing its stability. Further, NEDL1 is related to several cancers, including neuroblastomas, colorectal cancer and breast cancer, and it is also associated with some neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). The knowledge of NEDL1 and NEDL2 is important for revealing the mechanism of many human diseases.