@article {188,
	title = {Pten regulates Aurora-A and cooperates with Fbxw7 in modulating radiation-induced tumor development.},
	journal = {Mol Cancer Res},
	volume = {10},
	year = {2012},
	month = {2012 Jun},
	pages = {834-44},
	abstract = {<p>The Aurora-A kinase gene is frequently amplified and/or overexpressed in a variety of human cancers, leading to major efforts to develop therapeutic agents targeting this pathway. Here, we show that Aurora-A is targeted for ubiquitination and subsequent degradation by the F-box protein FBXW7 in a process that is regulated by GSK3β. Using a series of truncated Aurora-A proteins and site-directed mutagenesis, we identified distinct FBXW7 and GSK3β-binding sites in Aurora-A. Mutation of critical residues in either site substantially disrupts degradation of Aurora-A. Furthermore, we show that loss of Pten results in the stabilization of Aurora-A by attenuating FBXW7-dependent degradation of Aurora-A through the AKT/GSK3β pathway. Moreover, radiation-induced tumor latency is significantly shortened in Fbxw7(+/-)Pten(+/-) mice as compared with either Fbxw7(+/-) or Pten(+/-) mice, indicating that Fbxw7 and Pten appear to cooperate in suppressing tumorigenesis. Our results establish a novel posttranslational regulatory network in which the Pten and Fbxw7 pathways appear to converge on the regulation of Aurora-A level.</p>},
	keywords = {Animals, Aurora Kinase A, Aurora Kinases, Binding Sites, Blotting, Western, Cell Line, F-Box Proteins, Female, Gamma Rays, Glycogen Synthase Kinase 3, HCT116 Cells, HEK293 Cells, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutation, Neoplasms, Radiation-Induced, NIH 3T3 Cells, Protein Binding, Protein-Serine-Threonine Kinases, PTEN Phosphohydrolase, Time Factors, Ubiquitin, Ubiquitin-Protein Ligases},
	issn = {1557-3125},
	doi = {10.1158/1541-7786.MCR-12-0025},
	author = {Kwon, Yong-Won and Kim, Il-Jin and Wu, Di and Lu, Jing and Stock, William A and Liu, Yueyong and Huang, Yurong and Kang, Hio Chung and DelRosario, Reyno and Jen, Kuang-Yu and Perez-Losada, Jesus and Wei, Guangwei and Balmain, Allan and Jiang-Hua Mao}
}
