ZEB1 protein is a zinc finger transcription factor containing two zinc finger clusters that are crucial for its DNA-binding activity. It has its own protein-interacting domain, showing affinity toward Smad, CtBP, and p300-p/CAF. ZEB1 regulates targeted gene expression both positively and negatively by recruiting its cofactors. For example, it transcriptionally represses the CDH1 gene (E-cadherin) by interacting with its promoters and associating with CtBP transcriptional corepressors, followed by the recruitment of the SWI/SNF chromatin-remodeling protein BRG1, which further represses CDH1 gene expression and induces the progression of epithelial-mesenchymal transition (EMT). Conversely, ZEB1 positively regulates TGF-尾 downstream gene expression by interacting with p300-P/CAF and Smad proteins, promoting osteoblastic differentiation. Abnormal expression of ZEB1 is associated with many cancers, such as pancreatic cancer, osteosarcoma, lung cancer, liver cancer, colon cancer, gastric cancer, and breast cancers. In these cancers, increased expression of ZEB1 correlates with downregulation of E-cadherin and is related to advanced stages of cancer metastasis
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