Multifunctional human transcriptional coactivator protein PC4 is a substrate of Aurora kinases and activates the Aurora enzymes
| Autor: | Udaykumar Ranga, Mahesh Bachu, Kazuhiko Igarashi, Tapas K. Kundu, Amrutha Swaminathan, Karthigeyan Dhanasekaran, Sujata Kumari, Hiroki Shima, Ramachandran Boopathi |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Molecular Sequence Data Aurora B kinase Aurora inhibitor Mitosis macromolecular substances Biology Biochemistry Substrate Specificity 03 medical and health sciences Aurora kinase Coactivator Aurora Kinase B Humans Amino Acid Sequence Phosphorylation Kinase activity Molecular Biology Aurora Kinase A Cell Biology Recombinant Proteins Cell biology DNA-Binding Proteins Enzyme Activation Kinetics enzymes and coenzymes (carbohydrates) Spindle checkpoint HEK293 Cells 030104 developmental biology Gene Knockdown Techniques Transcription Factors |
| Zdroj: | FEBS Journal. 283:968-985 |
| ISSN: | 1742-464X |
| DOI: | 10.1111/febs.13653 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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