Proteasome-dependent degradation of transcription factor activating enhancer-binding protein 4 (TFAP4) controls mitotic division.

Journal article

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.

Authors: D'Annibale, S; Kim, J; Magliozzi, R; Low, T; Mohammed, S

• Publication status: Published
• Publisher: American Society for Biochemistry and Molecular Biology Inc.
• Journal: Journal of biological chemistry
• Volume: 289
• Issue: 11
• Pages: 7730-7737
• Publication date: 2014-03-01
• DOI: 10.1074/jbc.m114.549535
• EISSN: 1083-351X
• ISSN: 0021-9258
• Language: English
• Keywords: Mass Spectrometry; Plasmids; Mitosis; DNA-Binding Proteins; HEK293 Cells; Proteasome Endopeptidase Complex; Mutation; Epithelial-Mesenchymal Transition; SKP Cullin F-Box Protein Ligases; Humans; Cell Proliferation; Phosphorylation; Transcription Factors; G2 Phase; DNA Damage; Gene Expression Regulation; Microscopy, Fluorescence; Cell Line, Tumor; Hela Cells