title: Phosphorylation of multifunctional nucleolar protein nucleophosmin (NPM1) by aurora kinase B is critical for mitotic progression.
abstract: The functional association of NPM1 with Aurora kinases is well documented. Surprisingly, although NPM1 is a well characterized phosphoprotein, it is unknown whether it is a substrate of Aurora kinases. We have found that Aurora kinases A and B can phosphorylate NPM1 at a single serine residue, Ser125, in vitro and in vivo. Phosphorylated-S125-NPM1 (pS125-NPM1) localizes to the midbody region during late cytokinesis where it colocalizes with Aurora B. The overexpression of mutant (S125A) NPM1 resulted in the deregulation of centrosome duplication and mitotic defects possibly due to cytokinesis failure. These data suggest that Aurora kinase B-mediated phosphorylation of NPM1 plays a critical role during mitosis, which could have wider implications in oncogenesis.
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, Karnataka, India.
authors.forename: Jayasha
authors.initials: J
authors.lastname: Shandilya
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, Karnataka, India.
authors.forename: Parijat
authors.initials: P
authors.lastname: Senapati
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, Karnataka, India.
authors.forename: Karthigeyan
authors.initials: K
authors.lastname: Dhanasekaran
authors.affiliation: Confocal Facility, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, Karnataka, India.
authors.forename: Suma S
authors.initials: SS
authors.lastname: Bangalore
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, Karnataka, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, Karnataka, India.
authors.forename: A Hari
authors.initials: AH
authors.lastname: Kishore
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, Karnataka, India.
authors.forename: Akshay
authors.initials: A
authors.lastname: Bhat
authors.affiliation: Bangalore Institute of Oncology, Bangalore 560027, Karnataka, India.
authors.forename: Gopinath S
authors.initials: GS
authors.lastname: Kodaganur
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, Karnataka, India. Electronic address: tapas@jncasr.ac.in.
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Kundu
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000737:chemistry; D064107:Aurora Kinase B / Q000737:chemistry / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009062:Mouth Neoplasms / Q000201:enzymology; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D000090243:Nucleophosmin; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D013692:Telophase
chemical_list: C000716967:NPM1 protein, human; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C576917:AURKA protein, human; C576921:AURKB protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B
keywords: Aurora kinases; Cytokinesis; Mitosis; Nucleophosmin; Phosphorylation; Serine threonine protein kinase