Aurora A is elevated in cancer cells due to inactivation of EF1A2 PTEN GSK3b regulated late S G2 phase specific degradation pathway

Elevated expression of Aurora kinase-A oncoprotein is detected in a subset of human cancers across different organ sites. The mechanism(s) underlying over expression of the protein in cancer cells have not been well elucidated. This study demonstrates that inactivation of a novel mechanism of EF1A2 regulated PTEN-GSK3β-SCF complex mediated Aurora-A protein degradation pathway in S-G2 phases of mitosis leads to enhanced stability/steady state level of Aurora-A in cancer cells. EEF1A2 regulates interaction of Aurora-A with activated PTEN, GSK3β, Neddylated CUL1 and FBXW7, promoting ubiquitination mediated degradation of Aurora-A that is rescued in EEF1A2 knockdown cells. Ectopic expression of EEF1A2, on the other hand, enhances formation of the complex with GSK3β mediated inactivating phosphorylation and reduction in Aurora-A protein, recapitulating the S-G2 phase events. Genetic …