含有Cullin Neddylation 1 (CUN1)结构域的缺陷1 (DCUN1D1)是Neddylation E3连接酶，这是一种类似于并与泛素蛋白酶体途径相似的翻译后修饰过程。虽然已在多种鳞状细胞癌中被证实为癌基因，但在前列腺癌(PCa)中，DCUN1D1的确切作用尚未得到充分探索。在这里，我们对DCUN1D1在PCa中的作用进行了调查，并证明了DCUN1D1在细胞系和人体组织样本中的上调。抑制DCUN1D1显著减少了PCa细胞的增殖和迁移，并明显抑制了小鼠异种移植瘤的形成。应用基因组学和蛋白组学方法，我们提供了有关DCUN1D1的作用机制的新信息。我们确定了CUL3、CUL4B、RBX1、CAND1和RPS19蛋白作为DCUN1D1结合伴侣。我们的分析还揭示了与细胞生长和增殖、发育、细胞死亡和癌症通路以及WNT/β-连环蛋白通路相关的基因失调，作为潜在的机制。抑制DCUN1D1通过磷酸化和降解使β-连环蛋白失活，抑制了β-连环蛋白的下游作用，减少其与Lef1在Lef1/TCF复合物中的相互作用，从而调控了Wnt靶基因表达。综上所述，我们的数据指出了DCUN1D1蛋白在PCa中的重要作用，可用于潜在的靶向治疗的探索。

Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) is an E3 ligase for the neddylation, a post-translational process similar to and occurring in parallel to ubiquitin proteasome pathway. Although established as an oncogene in a variety of squamous cell carcinomas, the precise role of DCUN1D1 in prostate cancer (PCa) has not been previously explored thoroughly. Here, we investigated the role of DCUN1D1 in PCa and demonstrated that DCUN1D1 is upregulated in cell lines as well as human tissue samples. Inhibition of DCUN1D1 significantly reduced PCa cell proliferation and migration and remarkably inhibited xenograft formation in mice. Applying both genomics and proteomics approaches, we provide novel information about the DCUN1D1 mechanism of action. We identified CUL3, CUL4B, RBX1, CAND1 and RPS19 proteins as DCUN1D1 binding partners. Our analysis also revealed the dysregulation of genes associated with cellular growth and proliferation, developmental, cell death and cancer pathways and the WNT/β-catenin pathway as potential mechanisms. Inhibition of DCUN1D1 leads to the inactivation of β-catenin through its phosphorylation and degradation which inhibits the downstream action of β-catenin, reducing its interaction with Lef1 in the Lef1/TCF complex that regulates Wnt target gene expression. Together our data point to an essential role of the DCUN1D1 protein in PCa which can be explored for potential targeted therapy.