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Phosphorylation of p53 is regulated by TPX2-Aurora A in xenopus oocytes.

Abstract : p53 is an important tumor suppressor regulating the cell cycle at multiple stages in higher vertebrates. The p53 gene is frequently deleted or mutated in human cancers, resulting in loss of p53 activity. This leads to centrosome amplification, aneuploidy, and tumorigenesis, three phenotypes also observed after overexpression of the oncogenic kinase Aurora A. Accordingly, recent studies have focused on the relationship between these two proteins. p53 and Aurora A have been reported to interact in mammalian cells, but the function of this interaction remains unclear. We recently reported that Xenopus p53 can inhibit Aurora A activity in vitro but only in the absence of TPX2. Here we investigate the interplay between Xenopus Aurora A, TPX2, and p53 and show that newly synthesized TPX2 is required for nearly all Aurora A activation and for full p53 synthesis and phosphorylation in vivo during oocyte maturation. In vitro, phosphorylation mediated by Aurora A targets serines 129 and 190 within the DNA binding domain of p53. Glutathione S-transferase pull-down studies indicate that the interaction occurs via the p53 transactivation domain and the Aurora A catalytic domain around the T-loop. Our studies suggest that targeting of TPX2 might be an effective strategy for specifically inhibiting the phosphorylation of Aurora A substrates, including p53.
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Contributor : Hervé de Villemeur <>
Submitted on : Tuesday, August 25, 2009 - 4:56:41 PM
Last modification on : Thursday, February 25, 2021 - 7:02:18 PM

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Gaetan Pascreau, Frank Eckerdt, Andrea Lewellyn, Claude Prigent, James Maller. Phosphorylation of p53 is regulated by TPX2-Aurora A in xenopus oocytes.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (9), pp.5497-505. ⟨10.1074/jbc.M805959200⟩. ⟨inserm-00411055⟩



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