Human TPX2 is required for targeting Aurora-A kinase to the spindle

By T. Kufer, H. Silljé, R. Körner, O. Gruss, P. Meraldi, Erich A. Nigg. Journal of Cell Biology, 2002

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Aurora-A is a serine-threonine kinase implicated in the assembly and maintenance of the mitotic spindle. Here we show that human Aurora-A binds to TPX2, a prominent component of the spindle apparatus. TPX2 was identified by mass spectrometry as a major protein coimmunoprecipitating specifically with Aurora-A from mitotic HeLa cell extracts. Conversely, Aurora-A could be detected in TPX2 immunoprecipitates. This indicates that subpopulations of these two proteins undergo complex formation in vivo. Binding studies demonstrated that the NH2 terminus of TPX2 can directly interact with the COOH-terminal catalytic domain of Aurora-A. Although kinase activity was not required for this interaction, TPX2 was readily phosphorylated by Aurora-A. Upon siRNA-mediated elimination of TPX2 from cells, the association of Aurora-A with the spindle microtubules was abolished, although its association with spindle poles was unaffected. Conversely, depletion of Aurora-A by siRNA had no detectable influence on the localization of TPX2. We propose that human TPX2 is required for targeting Aurora-A kinase to the spindle apparatus. In turn, Aurora-A might regulate the function of TPX2 during spindle assembly.

Subfields: Cell Biology

View Paper: https://www.semanticscholar.org/paper/53ed6ea8feea0f0025c7728f246cbc4fbac26bc2

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Citations in the corpus

Gene Expression Signature of Cigarette Smoking and Its Role in Lung Adenocarcinoma Development and Survival (2008, background): “These genes, such as NEK2[11,12] and CENPF[11] (both on 1q32-q41), TPX2[13,14] and STK6 (or AURKA)[15] (related to the Aurora-A activation pathway important in tumor progression[16]), TTK (linked to cell mitosis through EGFR,[17] a critical drug target for lung adenocarcinoma[18]), and BIRC5 (Surviv”
The cellular geography of Aurora kinases (2003, background): “pl?Q9ULW0">TPX2 (targeting protein for XKLP2), which has been implicated in Aurora-A activation (see below), is required for the localization of the kinase to spindle microtubules, but not to SPINDLE POLES”
Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53 (2004, methodology): “We carried out siRNA experiments for aurora kinase A and Mdm2 as previously describe”
Aurora-A — A guardian of poles (2005, background): “TPX2 was found to interact with Aurora-A and to be not only a substrate but also an activator for Aurora-”
Roles of Aurora Kinases in Mitosis and Tumorigenesis (2007, background): “TPX2 is also required for targeting Aurora-A to the spindle (41, 42).”