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

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)7730-7
Aantal pagina's8
TijdschriftThe Journal of biological chemistry
Volume289
Nummer van het tijdschrift11
DOI's
StatusGepubliceerd - 14 mrt 2014

Vingerafdruk

Duik in de onderzoeksthema's van 'Proteasome-dependent degradation of transcription factor activating enhancer-binding protein 4 (TFAP4) controls mitotic division'. Samen vormen ze een unieke vingerafdruk.

Citeer dit