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RASSF1A interacts with and activates the mitotic kinase Aurora-A

Oncogene volume 27, pages 6175–6186 (2008)Cite this article

Abstract

The RAS association domain family 1A (RASSF1A) gene is located at chromosome 3p21.3 within a specific area of common heterozygous and homozygous deletions. RASSF1A frequently undergoes promoter methylation-associated inactivation in human cancers. Rassf1a−/− mice are prone to both spontaneous and carcinogen-induced tumorigenesis, supporting the notion that RASSF1A is a tumor suppressor. However, it is not fully understood how RASSF1A is involved in tumor suppression pathways. Here we show that overexpression of RASSF1A inhibits centrosome separation. RASSF1A interacts with Aurora-A, a mitotic kinase. Surprisingly, knockdown of RASSF1A by siRNA led to reduced activation of Aurora-A, whereas overexpression of RASSF1A resulted in increased activation of Aurora-A, suggesting that RASSF1A is involved in Aurora-A activation. Like other Aurora-A activators, RASSF1A was also a substrate of Aurora-A in vitro. The failure of recombinant RASSF1A to activate recombinant Aurora-A indicates that RASSF1A may not activate Aurora-A directly and suggests that RASSF1A may function as a scaffold to bring together Aurora-A and its activator(s). Inhibition of centrosome separation by RASSF1A overexpression is most likely a consequence of hyperstabilization of microtubules by this protein.

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Abbreviations

APC:

anaphase-promoting complex

DAPI:

4,6-diamidino-2-phenylindole

MBP:

maltose-binding protein

MEF:

mouse embryonic fibroblast

MTOC:

microtubule-organizing center

NORE:

novel Ras effector

RASSF1A:

RAS association domain family 1A

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Acknowledgements

We thank E Nigg and H Nojima for the Aurora-A and LATS2 plasmid constructs.

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Authors and Affiliations

  1. Division of Biology, Beckman Research Institute, City of Hope Cancer Center, Duarte, CA, USA

    L Liu, C Guo, S Tommasi & G P Pfeifer

  2. Institute of Genetics, University of Giessen, Giessen, Germany

    R Dammann

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  2. C Guo
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Correspondence to G P Pfeifer.

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Liu, L., Guo, C., Dammann, R. et al. RASSF1A interacts with and activates the mitotic kinase Aurora-A. Oncogene 27, 6175–6186 (2008). https://doi.org/10.1038/onc.2008.220

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