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Front Oncol. 2011 Dec 14;1:50. doi: 10.3389/fonc.2011.00050. eCollection 2011.

A SUMOylation Motif in Aurora-A: Implications for Spindle Dynamics and Oncogenesis.

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1
Molecular Oncology Programme, Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas Madrid, Spain.

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-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.

KEYWORDS:

Aurora-A; SUMO; cancer; kinases; mitosis; spindle

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