WDR79蛋白属于WD重复蛋白家族成员，含有六个WD基序，在进化中高度保守。然而，至今WDR79蛋白在肿瘤细胞内的功能和作用机制仍然知之甚少。在前期探索性研究中，我们发现与正常黑色素细胞相比，WDR79在多种黑色素瘤细胞中高表达，而且过表达WDR79促进黑色瘤细胞的增殖。为了探寻WDR79促黑色素瘤细胞增殖的分子机制，我们通过免疫共沉淀以及GST Pull-down实验证明WDR79与去泛素化酶HAUSP直接相互作用，其上调Mdm2和下调p53的功能，促使我们推测WDR79很可能在细胞内形成WDR79-HAUSP-Mdm2三元复合物，选择性促进HAUSP与其底物Mdm2的结合，去泛素化并稳定Mdm2，进而导致抑瘤蛋白p53的泛素化降解和功能活性降低，从而促进黑色素细胞的增殖。本项目对上述科学假说的验证，将揭示WDR79促进黑色素瘤细胞增殖的分子机制，为靶向性抗肿瘤治疗提供新的靶标和切入点。

WDR79, a member of the WD repeat family of proteins, bear six WD-repeat motif whose homologs have high sequence identities in yeast to human. However, the molecular mechanisms of WDR79 in tumorigenesis have so far not yet been clarified. In previous studies, we found that high expression of WDR79 present in melanoma cells compared to normal melanocytes and overexpressed WDR79 promoted the proliferation of melanoma cells. To probe the molecular mechanisms of WDR79, we identified WDR79 directly interacted with deubiquitylase HAUSP by co-immunoprecipitation and GST pull-down. Based on the function of upregulated Mdm2 and downregulated p53 in melanoma cells, we postulate WDR79-HAUSP-Mdm2 tenary complex is present in melanoma cells and promote the binding of HAUSP to Mdm2.This event in turn increases the stability and prolongs the half-life of Mdm2 via decreasing ubiquitination and results in decrease of functional activation and degradation of tumor suppressor p53.All of these will contribute to the proliferation of melanoma cells. The hypothesis verification in this project will reveal the molecular mechanisms of WDR79 in promoting melanoma cells proliferation and point to new avenues in targeted therapy for melanoma.