title: Multifunctional human transcriptional coactivator protein PC4 is a substrate of Aurora kinases and activates the Aurora enzymes.
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.
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, Karnataka, India.
authors.forename: Karthigeyan
authors.initials: K
authors.lastname: Dhanasekaran
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, Karnataka, India.
authors.forename: Sujata
authors.initials: S
authors.lastname: Kumari
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, Karnataka, India.
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Boopathi
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.|Center for Regulatory Epigenome and Diseases, Tohoku University, Sendai, Japan.|CREST, Japan Science and Technology Agency, Sendai, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shima
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, Karnataka, India.
authors.forename: Amrutha
authors.initials: A
authors.lastname: Swaminathan
authors.affiliation: Molecular Virology Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, Karnataka, India.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Bachu
authors.affiliation: Molecular Virology Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, Karnataka, India.
authors.forename: Udaykumar
authors.initials: U
authors.lastname: Ranga
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.|Center for Regulatory Epigenome and Diseases, Tohoku University, Sendai, Japan.|CREST, Japan Science and Technology Agency, Sendai, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, Karnataka, India.
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Kundu
mesh_terms: D000595:Amino Acid Sequence; D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism*; D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; C509201:SUB1 protein, human; D014157:Transcription Factors; C576917:AURKA protein, human; C576921:AURKB protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B
keywords: Aurora kinase; cell cycle; cytokinesis; positive coactivator 4; spindle organization