title: Aurora-C Interactions with Survivin and INCENP Reveal Shared and Distinct Features Compared with Aurora-B Chromosome Passenger Protein Complex.
abstract: Aurora-C, a member of the Aurora kinase family that can complement Aurora-B function in mitosis is either moderately expressed or repressed in most adult somatic tissues but is active in early embryonic development and expressed at elevated levels in multiple human cancers. Aurora-C overexpression reportedly plays a role in tumorigenic transformation. We performed detailed characterization of Aurora-C interactions with members of the Chromosome Passenger Complex (CPC), Survivin and Inner Centromere Protein (INCENP) in reference to known Aurora-B interactions to understand the functional significance of Aurora-C overexpression in human cancer cells. The results revealed that silencing of Aurora-C or -B individually does not affect localization of the other kinase and the two kinases exist predominantly in independent complexes in vivo. Presence of Aurora-C and -B in molecular complexes of varying as well as overlapping sizes and co-existence in INCENP overexpressing cells indicated oligomerization of ternary complexes under different physiological conditions in vivo. Furthermore, Aurora-C and -B stabilized INCENP through interaction with and phosphorylation of the IN box domain while Aurora-C was activated following Survivin phosphorylation on Serine 20. Phosphorylation of Survivin residue Serine 20 by Aurora-C and -B appears important for proper chromosome segregation. Taken together, our study suggests that Aurora-C, expressed at low levels in somatic cells, functions as a catalytic component of the CPC together with Aurora-B through mitosis. Elevated expression of Aurora-C in cancer cells alters the structural and functional characteristics of the Aurora-B-CPC leading to chromosomal instability.
authors.affiliation: Department of Translational Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Kaori
authors.initials: K
authors.lastname: Sasai
authors.affiliation: Department of Translational Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katayama
authors.affiliation: Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: David H
authors.initials: DH
authors.lastname: Hawke
authors.affiliation: Department of Translational Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Subrata
authors.initials: S
authors.lastname: Sen
mesh_terms: D000595:Amino Acid Sequence; D064107:Aurora Kinase B / Q000737:chemistry / Q000378:metabolism*; D064108:Aurora Kinase C / Q000737:chemistry / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism*; D020090:Chromosome Segregation; D017124:Conserved Sequence; D048749:Cytokinesis; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D055550:Protein Stability; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; C083767:INCENP protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D010768:Phosphoserine; D064107:Aurora Kinase B; D064108:Aurora Kinase C