Proteasome-dependent Degradation of Transcription Factor AP4 (TFAP4) Controls Mitotic Division [Cell Biology]

February 5th, 2014 by D'Annibale, S., Kim, J., Magliozzi, R., Low, T. Y., Mohammed, S., Heck, A. J. R., Guardavaccaro, D.

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 upregulated 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 leads 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.