文章：

抗肿瘤肽M1-20通过CUL4-DDB1-DCAF1介导的泛素化诱导CDK1降解

The antitumor peptide M1-20 induced the degradation of CDK1 through CUL4-DDB1-DCAF1-involved ubiquitination 

原文发布日期：2024-11-20

英文摘要：

CDK1 is an oncogenic serine/threonine kinase known to play an important role in the regulation of the cell cycle. FOXM1, as one of the CDK1 substrates, requires binding of CDK1/CCNB1 complex for phosphorylation-dependent recruitment of p300/CBP coactivators to mediate transcriptional activity. Previous studies from our laboratory found that a novel peptide (M1-20) derived from the C-terminus of FOXM1 exhibited potent inhibitory effects for cancer cells. Based on these proofs and to explore the inhibitory mechanism of M1-20, we designed experiments and found that CDK1 served as an important target of M1-20. M1-20 enhanced the ubiquitination and degradation of CDK1 by CUL4-DDB1-DCAF1 complexes through the proteasome pathway. M1-20 could also affect the formation of CDK1/CCNB1 complexes. In addition, compared to RO3306, a CDK1 inhibitor, M1-20 exhibited excellent inhibitory effects in FVB/N MMTV-PyVT murine model of spontaneous breast cancer. These results suggested that M1-20 was a potential CDK1 inhibitor for the treatment of cancer. 

摘要翻译：

CDK1是一种致癌性丝氨酸/苏氨酸激酶，已知在细胞周期调控中发挥重要作用。作为CDK1底物之一的FOXM1，需要与CDK1/CCNB1复合物结合以实现p300/CBP共激活因子的磷酸化依赖性招募，从而介导转录活性。我们实验室先前研究发现，源自FOXM1 C末端的新型肽段M1-20对癌细胞表现出强效抑制作用。基于这些证据，为探索M1-20的抑制机制，我们设计实验发现CDK1是M1-20的重要作用靶点。M1-20通过蛋白酶体途径增强CUL4-DDB1-DCAF1复合物对CDK1的泛素化修饰和降解过程，同时还能影响CDK1/CCNB1复合物的形成。此外，与CDK1抑制剂RO3306相比，M1-20在FVB/N MMTV-PyVT自发性乳腺癌小鼠模型中展现出更优异的抑制效果。这些结果表明M1-20是一种具有癌症治疗潜力的CDK1抑制剂。

原文链接：

The antitumor peptide M1-20 induced the degradation of CDK1 through CUL4-DDB1-DCAF1-involved ubiquitination