Functional characterization of AIBp, a novel Aurora-A binding protein in centrosome structure and spindle formation.
Aurora-A is involved in chromosome alignment, centrosome maturation, mitotic spindle assembly and regards to an oncogene. Aurora-A is also known to bind to several other proteins affecting its up-regulation or down-regulation and localization. However, how these different binding signals work together to regulate Aurora-A is not properly known. To explore ... more Aurora-A interacting proteins, the low-copy yeast two-hybrid screening using Aurora-A as bait protein was performed. One novel gene, AIBp, was demonstrated to associate with Aurora-A by the yeast two-hybrid method and in vitro GST pull-down assay. Molecular characterization showed that AIBp possessed a binding site at the C-terminal with Aurora-A (kinase domain). Interestingly, AIBp also interacts with hNinein at the N-terminal, which overlaps with a previously reported hNinein and GSK3beta binding site. Using a kinase assay, AIBp interacts with the Aurora-A kinase domain functions as a positive regulator, whereas AIBp binding to hNinein appears to block the phosphorylation of hNinein by both Aurora-A and GSK3beta. siRNA-mediated elimination of AIBp from HeLa cells, results in a doughnut-like shape, asymmetrical spindle pole and multiple spindle pole formation. We also demonstrated that both AIBp and Aurora-A are co-overexpressed in various brain tumors. These studies demonstrate that AIBp may not only be required for the dynamic movement of Aurora-A at the centrosomes and spindle apparatus during the cell cycle, but may also be important during brain tumorigenesis.
Mesh Terms:
Amino Acid Sequence, Aurora Kinases, Base Sequence, Brain Neoplasms, Carcinoma, Carrier Proteins, Centrosome, Cytoskeletal Proteins, DNA-Binding Proteins, Female, HeLa Cells, Humans, Male, Microtubule-Associated Proteins, Models, Biological, Molecular Sequence Data, Nuclear Proteins, Protein Binding, Protein Interaction Domains and Motifs, Protein-Serine-Threonine Kinases, Spindle Apparatus, Tissue Distribution, Two-Hybrid System Techniques
Amino Acid Sequence, Aurora Kinases, Base Sequence, Brain Neoplasms, Carcinoma, Carrier Proteins, Centrosome, Cytoskeletal Proteins, DNA-Binding Proteins, Female, HeLa Cells, Humans, Male, Microtubule-Associated Proteins, Models, Biological, Molecular Sequence Data, Nuclear Proteins, Protein Binding, Protein Interaction Domains and Motifs, Protein-Serine-Threonine Kinases, Spindle Apparatus, Tissue Distribution, Two-Hybrid System Techniques
Int. J. Oncol.
Date: Aug. 01, 2010
PubMed ID: 20596670
View in: Pubmed Google Scholar
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