Two newly identified sites in the N-terminal regulatory domain of Aurora-A are essential for auto-inhibition.
Biotechnol Lett
; 36(8): 1595-604, 2014 Aug.
Article
en En
| MEDLINE
| ID: mdl-24682789
ABSTRACT
Aurora-A, a centrosome-localized serine/threonine kinase, is over-expressed in multiple human cancers. We previously reported Zhang et al. (Biochem Biophys Res Commun 2007, 357347-352) intramolecular inhibitory regulation of Aurora-A between its N-terminal (Nt) regulatory domain (amino acids 1-128, Nt) and C-terminal catalytic domain (aa 129-403, Cd). Here, we identified two essential sites located on the Nt of Aurora-A (Lys 99 and Lys 119) and demonstrate that mutation of either residue to Gly could cause the Nt and C-terminal lobes of the catalytic domain in Aurora-A to form a closed conformation, resulting in a loss of kinase activity. This inactive conformation was reversed by adding C26 peptide (274-299) or Ajuba, which is a required activator of Aurora-A. Over-expression of either mutant induced G2/M arrest. These results provide a basis for future anti-cancer studies targeting Aurora-A.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Aurora Quinasa A
Límite:
Humans
Idioma:
En
Revista:
Biotechnol Lett
Año:
2014
Tipo del documento:
Article