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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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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DOI: https://doi.org/10.1038/onc.2008.220
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