A SUMOylation Motif in Aurora-A: Implications for Spindle Dynamics and Oncogenesis.
Aurora-A is a serine/threonine kinase that plays critical roles in centrosome maturation, spindle dynamics, and chromosome orientation and it is frequently over-expressed in human cancers. In this work, we show that Aurora-A interacts with the SUMO-conjugating enzyme UBC9 and co-localizes with SUMO1 in mitotic cells. Aurora-A can be SUMOylated in vitro and in vivo. Mutation of the highly conserved SUMOylation residue lysine 249 significantly disrupts Aurora-A SUMOylation and mitotic defects characterized by defective and multipolar spindles ensue. The Aurora-A(K249R) mutant has normal kinase activity but displays altered dynamics at the mitotic spindle. In addition, ectopic expression of the Aurora-A(K249R) mutant results in a significant increase in susceptibility to malignant transformation induced by the Ras oncogene. These data suggest that modification by SUMO residues may control Aurora-A function at the spindle and that deficiency of SUMOylation of this kinase may have important implications for tumor development.
Molecular Oncology Programme, Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas Madrid, Spain.
Ignacio
I
Pérez de Castro
Cristina
C
Aguirre-Portolés
Benedicte
B
Martin
Gonzalo
G
Fernández-Miranda
Andrea
A
Klotzbucher
Michael H G
MH
Kubbutat
Diego
D
Megías
Yannick
Y
Arlot-Bonnemains
Marcos
M
Malumbres