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

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 -