Proteasome-dependent Degradation of Transcription Factor Activating Enhancer-binding Protein 4 (TFAP4) Controls Mitotic Division
pmid: 24500709
pmc: PMC3953283
Proteasome-dependent Degradation of Transcription Factor Activating Enhancer-binding Protein 4 (TFAP4) Controls Mitotic Division
TFAP4, a basic helix-loop-helix transcription factor that regulates the expression of a multitude of genes involved in the regulation of cellular proliferation, stemness, and epithelial-mesenchymal transition, is up-regulated in colorectal cancer and a number of other human malignancies. We have found that, during the G2 phase of the cell division cycle, TFAP4 is targeted for proteasome-dependent degradation by the SCF(βTrCP) ubiquitin ligase. This event requires phosphorylation of TFAP4 on a conserved degron. Expression of a stable TFAP4 mutant unable to interact with βTrCP results in a number of mitotic defects, including chromosome missegregation and multipolar spindles, which eventually lead to the activation of the DNA damage response. Our findings reveal that βTrCP-dependent degradation of TFAP4 is required for the fidelity of mitotic division.
- University of Verona Italy
- Utrecht University Netherlands
- Hubrecht Institute for Developmental Biology and Stem Cell Research Netherlands
- University of Oxford United Kingdom
- University Museum Utrecht Netherlands
G2 Phase, Proteasome Endopeptidase Complex, Epithelial-Mesenchymal Transition, Mitosis, Fluorescence, Mass Spectrometry, Cell Line, SDG 3 - Good Health and Well-being, Cell Line, Tumor, Humans, Phosphorylation, Cell Proliferation, Microscopy, Tumor, SKP Cullin F-Box Protein Ligases, DNA-Binding Proteins, HEK293 Cells, Gene Expression Regulation, Microscopy, Fluorescence, Mutation, BetaTrCP; Cell Cycle; E3 Ubiquitin Ligase; Mitosis; Protein Degradation; TFAP4; Ubiquitin; Cell Line, Tumor; Cell Proliferation; DNA Damage; DNA-Binding Proteins; Epithelial-Mesenchymal Transition; G2 Phase; HEK293 Cells; HeLa Cells; Humans; Mass Spectrometry; Microscopy, Fluorescence; Mutation; Phosphorylation; Plasmids; Proteasome Endopeptidase Complex; SKP Cullin F-Box Protein Ligases; Transcription Factors; Gene Expression Regulation; Mitosis, DNA Damage, HeLa Cells, Plasmids, Transcription Factors
G2 Phase, Proteasome Endopeptidase Complex, Epithelial-Mesenchymal Transition, Mitosis, Fluorescence, Mass Spectrometry, Cell Line, SDG 3 - Good Health and Well-being, Cell Line, Tumor, Humans, Phosphorylation, Cell Proliferation, Microscopy, Tumor, SKP Cullin F-Box Protein Ligases, DNA-Binding Proteins, HEK293 Cells, Gene Expression Regulation, Microscopy, Fluorescence, Mutation, BetaTrCP; Cell Cycle; E3 Ubiquitin Ligase; Mitosis; Protein Degradation; TFAP4; Ubiquitin; Cell Line, Tumor; Cell Proliferation; DNA Damage; DNA-Binding Proteins; Epithelial-Mesenchymal Transition; G2 Phase; HEK293 Cells; HeLa Cells; Humans; Mass Spectrometry; Microscopy, Fluorescence; Mutation; Phosphorylation; Plasmids; Proteasome Endopeptidase Complex; SKP Cullin F-Box Protein Ligases; Transcription Factors; Gene Expression Regulation; Mitosis, DNA Damage, HeLa Cells, Plasmids, Transcription Factors
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