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Potential involvement of RITA in the activation of Aurora A at spindle poles during mitosis

Oncogene volume 38, pages 4199–4214 (2019)Cite this article

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Abstract

The mitotic kinase Aurora A is crucial for various mitotic events. Its activation has been intensively investigated and is not yet completely understood. RITA, the RBP-J interacting and tubulin-associated protein, has been shown to modulate microtubule dynamics in mitosis. We asked if RITA could be related to the activation of Aurora A. We show here that RITA is colocalized with Aurora A and its activator TPX2 at spindle poles during mitosis. FLAG-RITA is precipitated with the complex of Aurora A, TPX2 and tubulin. Depletion of RITA increases exclusively active Aurora A and TPX2 at spindle poles in diverse cancer cell lines and in RITA knockout mouse embryonic fibroblasts. The enhanced active Aurora A, its substrate p-TACC3 and TPX2 are restored by adding back of RITA but not its Δtub mutant with an impaired tubulin-binding capability, indicating that RITA’s role as Aurora A’s modulator is mediated through its interaction with tubulin. Also, the mitotic failures in cells depleted of RITA are rescued by the inhibition of Aurora A. RITA itself does not directly interfere with the catalytic activity of Aurora A, instead, affects the microtubule binding of its activator TPX2. Moreover, Aurora A's activation correlates with microtubule stabilization induced by the microtubule stabilizer paclitaxel, implicating that stabilized microtubules caused by RITA depletion could also account for increased active Aurora A. Our data suggest a potential role for RITA in the activation of Aurora A at spindle poles by modulating the microtubule binding of TPX2 and the microtubule stability during mitosis.

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Acknowledgements

We gratefully thank Ms. Friemel (Frankfurt) and Ms. Schirmer (Ulm) for their technical assistance. The work was partially supported by the Deutsche Forschungsgemeinschaft (SFB1074/A3 to FO, Yu 156/7-1 to JY) and the BMBF (research nucleus SyStAR to FO). PK was supported by the International Graduate School in Molecular Medicine, Ulm (GSC270).

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  1. Kerstin Steinhäuser

    Present address: Solvadis distribution GmbH, Am Hafen 4, 64579, Gernsheim, Germany

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  1. Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, Theodor-Stern-Kai 7, D-60590, Frankfurt, Germany

    Nina-Naomi Kreis, Kerstin Steinhäuser, Andreas Ritter, Samira Catharina Hoock, Susanne Roth, Frank Louwen & Juping Yuan

  2. Department of Internal Medicine I, University Medical Center Ulm, Center for Internal Medicine, Albert-Einstein-Allee 23, D-89081, Ulm, Germany

    Patricia Klöble & Franz Oswald

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Kreis, NN., Steinhäuser, K., Ritter, A. et al. Potential involvement of RITA in the activation of Aurora A at spindle poles during mitosis. Oncogene 38, 4199–4214 (2019). https://doi.org/10.1038/s41388-019-0716-7

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