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- Title
RASSF1A interacts with and activates the mitotic kinase Aurora-A.
- Authors
Liu, L.; Guo, C.; Dammann, R.; Tommasi, S.; Pfeifer, G. P.
- 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.Oncogene (2008) 27, 6175–6186; doi:10.1038/onc.2008.220; published online 21 July 2008
- Subjects
RAS oncogenes; GUANOSINE triphosphatase genes; TUMOR suppressor genes; CHROMOSOMES; METHYLATION; CENTROSOMES; ORGANELLES; CANCER genetics
- Publication
Oncogene, 2008, Vol 27, Issue 47, p6175
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2008.220