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

Sara D'Annibale1, Jihoon Kim, Roberto Magliozzi

  • 1From the Hubrecht Institute-KNAW and University Medical Center Utrecht.

The Journal of Biological Chemistry
|February 7, 2014
PubMed

Insights

Transcription factor AP4 (TFAP4) degradation by SCF(βTrCP) is crucial for accurate cell division. This process prevents mitotic errors like chromosome missegregation, ensuring genomic stability in cancer cells.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Transcription factor AP4 (TFAP4) regulates genes involved in proliferation, stemness, and epithelial-mesenchymal transition.
  • TFAP4 is frequently upregulated in colorectal cancer and other malignancies.

Purpose of the Study:

  • To investigate the regulation of TFAP4 during the cell cycle.
  • To determine the role of TFAP4 degradation in mitotic fidelity.

Main Methods:

  • Utilized cell cycle synchronization and proteasome inhibition assays.
  • Employed stable TFAP4 mutants to assess the impact on mitosis.
  • Analyzed chromosome segregation and spindle formation.

Main Results:

  • TFAP4 undergoes SCF(βTrCP)-mediated proteasomal degradation during the G2 phase, dependent on phosphorylation.
  • Expression of a non-degradable TFAP4 mutant induced mitotic defects, including chromosome missegregation and multipolar spindles.
  • These defects activated the DNA damage response.

Conclusions:

  • SCF(βTrCP)-dependent degradation of TFAP4 is essential for maintaining the fidelity of mitotic division.
  • Targeting TFAP4 degradation may offer a therapeutic strategy for cancers with high TFAP4 expression.
Keywords:
BetaTrCPCell CycleE3 Ubiquitin LigaseMitosisProtein DegradationTFAP4Ubiquitin

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