title: A novel role for TPX2 as a scaffold and co-activator protein of the Chromosomal Passenger Complex.
abstract: Aurora B kinase forms the enzymatic core of the Chromosomal Passenger Complex (CPC) and is a master regulator of mitosis. Understanding the regulation of Aurora B is critical to illuminate its role in mitosis. INCENP, Survivin and Borealin have all been known to promote Aurora B activation. In this study, we have identified the Aurora A activator protein TPX2 as a novel scaffold and co-activator protein of the CPC. Studies utilizing M-phase Xenopus egg extracts (XEE) revealed that the immunodepletion of endogenous TPX2 from XEE decreases Aurora B-Survivin and Aurora B-INCENP interactions, leading to a consequent reduction in Aurora B activity. Further, residues 138 to 328 of Xenopus TPX2 (TPX2 B) are sufficient to enhance Aurora B-Survivin association and Aurora B kinase activity in vitro. Importantly, experiments with pancreatic cancer cell lines suggest that this mechanism of Aurora B activation by TPX2 is likely to be conserved in human cells. Strikingly, the overexpression of human TPX2 B in HeLa cells causes defects in metaphase chromosome alignment and INCENP localization. Thus, in addition to its already established role as an Aurora A activator, our data support the role of TPX2 as a novel co-activator of Aurora kinase B.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-7696, USA.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Iyer
authors.forename: Ming-Ying
authors.initials: MY
authors.lastname: Tsai
mesh_terms: D000818:Animals; D064107:Aurora Kinase B / Q000302:isolation & purification / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000302:isolation & purification / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000302:isolation & purification / Q000378:metabolism*; D008938:Mitosis; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism*; D014981:Xenopus
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C083767:INCENP protein, human; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C122167:TPX2 protein, human; C576921:AURKB protein, human; D064107:Aurora Kinase B