Journal article

RASSF1A interacts with and activates the mitotic kinase Aurora-A


Authors listLiu, L; Guo, C; Dammann, R; Tommasi, S; Pfeifer, GP

Publication year2008

Pages6175-6186

JournalOncogene

Volume number27

Issue number47

ISSN0950-9232

eISSN1476-5594

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

PublisherSpringer Nature [academic journals on nature.com]


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.




Citation Styles

Harvard Citation styleLiu, L., Guo, C., Dammann, R., Tommasi, S. and Pfeifer, G. (2008) RASSF1A interacts with and activates the mitotic kinase Aurora-A, Oncogene, 27(47), pp. 6175-6186. https://doi.org/10.1038/onc.2008.220

APA Citation styleLiu, L., Guo, C., Dammann, R., Tommasi, S., & Pfeifer, G. (2008). RASSF1A interacts with and activates the mitotic kinase Aurora-A. Oncogene. 27(47), 6175-6186. https://doi.org/10.1038/onc.2008.220


Last updated on 2025-21-05 at 15:19