Proteasome-dependent degradation of transcription factor activating enhancer-binding protein 4 (TFAP4) controls mitotic division
D'Annibale, Sara; Kim, Jihoon; Magliozzi, Roberto; Low, Teck Yew; Mohammed, Shabaz; Heck, Albert J R; Guardavaccaro, Daniele
(2014) Journal of Biological Chemistry, volume 289, issue 11, pp. 7730 - 7
(Article)
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
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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.
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Keywords: Cell Line, Tumor, Cell Proliferation, DNA Damage, DNA-Binding Proteins, Epithelial-Mesenchymal Transition, G2 Phase, Gene Expression Regulation, HEK293 Cells, HeLa Cells, Humans, Mass Spectrometry, Microscopy, Fluorescence, Mitosis, Mutation, Phosphorylation, Plasmids, Proteasome Endopeptidase Complex, SKP Cullin F-Box Protein Ligases, Transcription Factors
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology Inc.
(Peer reviewed)
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