Multifunctional human transcriptional coactivator protein PC 4 is a substrate of Aurora kinases and activates the Aurora enzymes

Positive coactivator 4 ( PC 4), a human transcriptional coactivator, 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 PC 4 outside the nuc...

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Bibliographic Details
Published in:The FEBS journal 2016-03, Vol.283 (6), p.968-985
Main Authors: Dhanasekaran, Karthigeyan, Kumari, Sujata, Boopathi, Ramachandran, Shima, Hiroki, Swaminathan, Amrutha, Bachu, Mahesh, Ranga, Udaykumar, Igarashi, Kazuhiko, Kundu, Tapas K.
Format: Article
Language:English
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Summary:Positive coactivator 4 ( PC 4), a human transcriptional coactivator, 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 PC 4 outside the nucleus upon nuclear envelope breakdown. A fraction of PC 4 associates with Aurora A and Aurora B and undergoes phosphorylation, following which PC 4 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 PC 4 knockdown cells where the defects are rescued only by the catalytically active Aurora kinases, but not the kinase‐dead mutants. Similarly, the PC 4 phosphodeficient mutant failed to rescue such defects. Hence, our observations establish a novel mitotic function of PC 4 that might be dependent on Aurora kinase‐mediated phosphorylation.
ISSN:1742-464X
1742-4658
DOI:10.1111/febs.13653