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

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

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)7730-7
Number of pages8
JournalThe Journal of biological chemistry
Volume289
Issue number11
DOIs
Publication statusPublished - 14 Mar 2014

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

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