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

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 SCFβTrCP 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)7730-7737
Number of pages8
JournalJournal of Biological Chemistry
Volume289
Issue number11
DOIs
Publication statusPublished - 14 Mar 2014
Externally publishedYes

Fingerprint

Activating Transcription Factors
Proteasome Endopeptidase Complex
Carrier Proteins
Degradation
Basic Helix-Loop-Helix Transcription Factors
Phosphorylation
Epithelial-Mesenchymal Transition
G2 Phase
Ligases
Chromosomes
Ubiquitin
DNA Damage
Colorectal Neoplasms
Cell Cycle
Transcription Factors
Genes
Chemical activation
Cells
Cell Proliferation
Defects

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Proteasome-dependent degradation of transcription factor activating enhancer-binding protein 4 (TFAP4) controls mitotic division. / D'Annibale, Sara; Kim, Jihoon; Magliozzi, Roberto; Teck Yew, Low; Mohammed, Shabaz; Heck, Albert J R; Guardavaccaro, Daniele.

In: Journal of Biological Chemistry, Vol. 289, No. 11, 14.03.2014, p. 7730-7737.

Research output: Contribution to journalArticle

D'Annibale, Sara ; Kim, Jihoon ; Magliozzi, Roberto ; Teck Yew, Low ; Mohammed, Shabaz ; Heck, Albert J R ; Guardavaccaro, Daniele. / Proteasome-dependent degradation of transcription factor activating enhancer-binding protein 4 (TFAP4) controls mitotic division. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 11. pp. 7730-7737.
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