Human Kruppel-like Factor 5 Is a Target of the E3 Ubiquitin Ligase WWP1 for Proteolysis in Epithelial Cells
Copyright policy )Human Kruppel-like Factor 5 Is a Target of the E3 Ubiquitin Ligase WWP1 for Proteolysis in Epithelial Cells
The transcription factor KLF5 plays an important role in human carcinogenesis. In epithelial cells, the KLF5 protein is tightly regulated by the ubiquitin-proteasome pathway. To better understand the mechanisms for the regulation of KLF5 protein, we identified and characterized an E3 ubiquitin ligase for KLF5, i.e. WWP1. We found that WWP1 formed a protein complex with KLF5 in vivo and in vitro. Furthermore, WWP1 mediated the ubiquitination and degradation of KLF5, and the catalytic cysteine residue of WWP1 is essential for its function. A PY motif in a transactivation domain of KLF5 is necessary for its interaction with WWP1. Finally, WWP1 was amplified and overexpressed in some cancer cell lines from the prostate and breast, which negatively regulated the function of KLF5 in gene regulation. These findings not only established WWP1 as an E3 ubiquitin ligase for KLF5, they also further implicated the KLF5 pathway in human carcinogenesis.
- University System of Ohio United States
- Emory University United States
- Nankai University China (People's Republic of)
- University of Cincinnati Medical Center United States
- University of Cincinnati United States
Male, Microscopy, Confocal, Amino Acid Motifs, Blotting, Western, Kruppel-Like Transcription Factors, Breast Neoplasms, Epithelial Cells, DNA, Catalysis, Gene Expression Regulation, Neoplastic, Gene Expression Regulation, Microscopy, Fluorescence, Cell Line, Tumor, Neoplasms, Humans, Immunoprecipitation, Female, Cysteine, Luciferases, Glutathione Transferase
Male, Microscopy, Confocal, Amino Acid Motifs, Blotting, Western, Kruppel-Like Transcription Factors, Breast Neoplasms, Epithelial Cells, DNA, Catalysis, Gene Expression Regulation, Neoplastic, Gene Expression Regulation, Microscopy, Fluorescence, Cell Line, Tumor, Neoplasms, Humans, Immunoprecipitation, Female, Cysteine, Luciferases, Glutathione Transferase
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