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Proteasome-dependent Degradation of Transcription Factor Activating Enhancer-binding Protein 4 (TFAP4) Controls Mitotic Division

Authors: D'Annibale, Sara; Kim, Jihoon; Magliozzi, Roberto; Low, Teck Yew; Mohammed, Shabaz; Heck, Albert J R; Guardavaccaro, Daniele;

Proteasome-dependent Degradation of Transcription Factor Activating Enhancer-binding Protein 4 (TFAP4) Controls Mitotic Division

Abstract

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.

Keywords

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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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
24
Top 10%
Top 10%
Top 10%
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