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.
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