CBP-mediated Slug acetylation stabilizes Slug and promotes EMT and migration of breast cancer cells.

Slug, a member of the Snail family of transcriptional repressors, plays a key role in cancer progression, cellular plasticity, and epithelial to mesenchymal transition (EMT). Slug is a fast-turnover protein and its stability is controlled by post-translational modifications. Here, we identified that Slug is acetylated by acetyltransferase CREB-binding protein (CBP) ...
in breast cancer cells. CBP directly interacts with the C-terminal domain of Slug through its catalytic histone acetyltransferase (HAT) domain, leading to acetylation of Slug at lysines 166 and 211. Analysis with acetylation-specific antibodies revealed that Slug is highly acetylated in metastatic breast cancer cells. Notably, Slug acetylation, mediated by CBP at lysines 166 and 211, doubles its half-life and increases its stability. Further, acetylated Slug downregulates the expression of E-cadherin, the epithelial marker, and upregulates the expression of N-cadherin and vimentin, thereby promoting breast cancer cell migration. In conclusion, the present study demonstrates that CBP-mediated Slug acetylation increases its stability, promoting EMT and migration of breast cancer cells.
Mesh Terms:
Acetylation, Amino Acid Sequence, Breast Neoplasms, CREB-Binding Protein, Cadherins, Cell Line, Tumor, Cell Movement, Epithelial-Mesenchymal Transition, Female, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, MCF-7 Cells, Protein Stability, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Amino Acid, Snail Family Transcription Factors
Sci China Life Sci
Date: Apr. 01, 2021
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