Nedd4家族E3泛素连接酶在肿瘤中的作用

More and more evidences indicated that E3 ubiquitin ligases played an important role in cancer development. So far as we know, there are nine members in Nedd4-like E3 family, with a similar structure including a C2 domain at the N-terminus, two to four WW domains in the middle, and a HECT domain at the C-terminus. It was reported that Nedd4 family were involved in tumorgenesis and development, such as WWP1 in breast and prostate cancer, Nedd4 in bladder and prostate cancer, Smurf2 in esophageal squamous cell carcinoma and Smurf1 in pancreatic cancer. Besides, Nedd4 family take parts in lysosomal or proteasomal degradation, ubiquitin-mediated protein trafficking, and nuclear translocation of multiple proteins, further on, they modulate important signaling pathways involved in tumorigenesis and development, like EGF, IGF, TGFβ, VEGF, TNFα, and SDF-1. Additionally, several members of Nedd4 family regulate various cancer-related transcription factors directly, like the Smads, KLF, RUNX, p53, and Jun. Moreover, multiple E3 of Nedd4 family shows ligase independent function. Furthermore, Nedd4 family is frequently regulated by ubiquitination, phosphorylation, translocation, and transcription in cancer cells. Since the regulation and biological output of these E3 ligases is a complex process, study of the role of these E3s in cancer development need more evidences. However, understanding the potential role of these E3 may facilitate the identification and development of drug and new biomarkers in human cancer.