Multifunctional Human Transcriptional Co-activator Protein PC4 is a Substrate of Aurora Kinases and Activates the Aurora Enzymes

The FEBS Journal
Karthigeyan DhanasekaranTapas K Kundu

Abstract

Human transcriptional co-activator PC4 is involved in diverse processes like chromatin organization and transcription regulation. It is hyperphosphorylated during mitosis, with unknown significance. For the first time, we demonstrate the function of PC4 outside the nucleus upon nuclear envelope breakdown. A fraction of PC4 associates with Aurora A and Aurora B and undergoes phosphorylation, following which, PC4 activates both Aurora A and B to sustain optimal kinase activity to maintain the phosphorylation gradient for the proper functioning of the mitotic machinery. This mitotic role is evident in PC4 knockdown cells where the defects are rescued only by the catalytically active Aurora kinases but not the kinase dead mutants. Similarly, the PC4 phosphodeficient mutant failed to rescue such defects. Hence, our observations establish a novel mitotic function of PC4 that might be dependent on Aurora kinase-mediated phosphorylation. This article is protected by copyright. All rights reserved.

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Citations

Apr 19, 2017·The Journal of Biological Chemistry·Wezley C GriffinKevin D Raney
Apr 14, 2017·Molecular Biology of the Cell·Mariah L HanleyTimothy J Mitchison
Jun 2, 2017·Current Genetics·Miguel Garavís, Olga Calvo

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