| First Author | Kiat LS | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 47 | Pages | 45558-65 |
| PubMed ID | 12244051 | Mgi Jnum | J:80203 |
| Mgi Id | MGI:2445268 | Doi | 10.1074/jbc.M206820200 |
| Citation | Kiat LS, et al. (2002) Aurora-A Kinase Interacting Protein (AIP), a Novel Negative Regulator of Human Aurora-A Kinase. J Biol Chem 277(47):45558-65 |
| abstractText | Aurora kinases have evolved as a new family of mitotic centrosome- and microtubule-associated kinases that regulate the structure and function of centrosomes and spindle. One of its members, Aurora-A, is a potential oncogene. Overexpression of Aurora-A is also implicated in defective centrosome duplication and segregation, leading to aneuploidy and tumorigenesis in various cancer cell types. However, the regulatory pathways for mammalian Aurora-A are not well understood. Exploiting the lethal phenotype associated with the overexpression of Aurora-A in yeast, we performed a dosage suppressor screen in yeast and report here the identification of a novel negative regulator of Aurora-A, named AIP (Aurora-A kinase Interacting Protein). AIP is a ubiquitously expressed nuclear protein that interacts specifically with human Aurora-A in vivo. Ectopic expression of AIP with Aurora-A in NIH 3T3 and COS cells results in the down-regulation of ectopically expressed Aurora-A protein levels, and this down-regulation is demonstrated to be the result of destabilization of Aurora-A through a proteasome-dependent protein degradation pathway. A noninteracting deletion mutant of AIP does not down-regulate Aurora-A protein, suggesting that the interaction is important for the protein degradation. AIP could therefore be a potential useful target gene for anti-tumor drugs. |
