期刊
FRONTIERS IN ONCOLOGY
卷 1, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2011.00050
关键词
mitosis; kinases; Aurora-A; SUMO; spindle; cancer
类别
资金
- Spanish Ministry of Science and Innovation
- Ramon y Cajal contract
- Association for International Cancer Research (AICR) [08-0188]
- Fundacion Raman Areces, Spanish Ministry of Science and Innovation (MICINN) [SAF2010-19710, SAF2009-07973, CSD2007-00017]
- Canceropole Grand Quest
- Institut Federalif de Recherches (IFR-Universite Rennes)
- Comunidad de Madrid, the OncoBIO ConsoliderIngenio [S-B10-02832006]
- European Union Seventh Framework Program [HEALTH -F5-2010-241548]
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 SUMO 1 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.
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