Functional characterization of AIBp, a novel Aurora-A binding protein in centrosome structure and spindle formation.

Abstract:

: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.

journal_name

Int J Oncol

authors

Lieu AS,Cheng TS,Chou CH,Wu CH,Hsu CY,Huang CY,Chang LK,Loh JK,Chang CS,Hsu CM,Howng SL,Hong YR

doi

10.3892/ijo_00000691

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

429-36

issue

2

eissn

1019-6439

issn

1791-2423

journal_volume

37

pub_type

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