AUTHOR=Pérez de Castro Ignacio , Aguirre-Portolés Cristina , Martin Benedicte , Fernández-Miranda Gonzalo , Klotzbucher Andrea , G. Kubbutat Michael H., Megías Diego , Arlot-Bonnemains Yannick , Malumbres Marcos TITLE=A SUMOylation Motif in Aurora-A: Implications for Spindle Dynamics and Oncogenesis JOURNAL=Frontiers in Oncology VOLUME=Volume 1 - 2011 YEAR=2011 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2011.00050 DOI=10.3389/fonc.2011.00050 ISSN=2234-943X ABSTRACT=

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-AK249R mutant has normal kinase activity but displays altered dynamics at the mitotic spindle. In addition, ectopic expression of the Aurora-AK249R 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.