Multifunctional human transcriptional coactivator protein PC4 is a substrate of Aurora kinases and activates the Aurora enzymes

Karthigeyan Dhanasekaran, Sujata Kumari, Ramachandran Boopathi, Hiroki Shima, Amrutha Swaminathan, Mahesh Bachu, Udaykumar Ranga, Kazuhiko Igarashi, Tapas K. Kundu

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)

Abstract

Positive coactivator 4 (PC4), 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 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.

Original languageEnglish
Pages (from-to)968-985
Number of pages18
JournalFEBS Journal
Volume283
Issue number6
DOIs
Publication statusPublished - 2016 Mar 1

Keywords

  • Aurora kinase
  • cell cycle
  • cytokinesis
  • positive coactivator 4
  • spindle organization

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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