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

doi:10.1074/jbc.M114.549535

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

24 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 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 language	English
Pages (from-to)	7730-7
Number of pages	8
Journal	The Journal of biological chemistry
Volume	289
Issue number	11
DOIs	https://doi.org/10.1074/jbc.M114.549535
Publication status	Published - 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

Access to Document

10.1074/jbc.M114.549535

Cite this

@article{b470dae0cec8450d9e5371ff62a9f834,

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

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.",

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",

author = "Sara D'Annibale and Jihoon Kim and Roberto Magliozzi and Low, {Teck Yew} and Shabaz Mohammed and Heck, {Albert J R} and Daniele Guardavaccaro",

year = "2014",

month = mar,

day = "14",

doi = "10.1074/jbc.M114.549535",

language = "English",

volume = "289",

pages = "7730--7",

journal = "The Journal of biological chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology Inc.",

number = "11",

}

TY - JOUR

T1 - Proteasome-dependent degradation of transcription factor activating enhancer-binding protein 4 (TFAP4) controls mitotic division

AU - D'Annibale, Sara

AU - Kim, Jihoon

AU - Magliozzi, Roberto

AU - Low, Teck Yew

AU - Mohammed, Shabaz

AU - Heck, Albert J R

AU - Guardavaccaro, Daniele

PY - 2014/3/14

Y1 - 2014/3/14

N2 - 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.

AB - 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.

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - DNA Damage

KW - DNA-Binding Proteins

KW - Epithelial-Mesenchymal Transition

KW - G2 Phase

KW - Gene Expression Regulation

KW - HEK293 Cells

KW - HeLa Cells

KW - Humans

KW - Mass Spectrometry

KW - Microscopy, Fluorescence

KW - Mitosis

KW - Mutation

KW - Phosphorylation

KW - Plasmids

KW - Proteasome Endopeptidase Complex

KW - SKP Cullin F-Box Protein Ligases

KW - Transcription Factors

U2 - 10.1074/jbc.M114.549535

DO - 10.1074/jbc.M114.549535

M3 - Article

C2 - 24500709

SN - 0021-9258

VL - 289

SP - 7730

EP - 7737

JO - The Journal of biological chemistry

JF - The Journal of biological chemistry

IS - 11

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this