Truncated RASSF7 promotes centrosomal defects and cell death

Tulay Gulsen, Irene Hadjicosti, Yueshi Li, Xinyun Zhang, Paul R. Whitley, Andrew D. Chalmers

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Abstract

RASSF7 protein localises to the centrosome and plays a key role in mitosis. Its expression is also increased in a range of tumour types. However, little is known about the molecular basis of RASSF7's function and it is not clear if it acts as an oncogene in the cancers where its levels are elevated. Here, we carry out the first analysis of the domains of rassf7, focusing on which of them are responsible for its localisation to the centrosome. Constructs were generated to allow the expression of a series of truncated versions of rassf7 and the level of centrosomal localisation shown by each protein quantified. This analysis was carried out in Xenopus embryos which are a tractable system where rassf7 localisation can easily be studied. Our data shows that the coiled-coil domain of rassf7 is required and sufficient to direct its centrosomal localisation. The RA domain did not appear to have a role in mediating localisation. Surprisingly, removal of the extreme C-terminus of the protein caused rassf7 to accumulate at the centrosome and drive centrosome defects, including accumulation of the centrosomal protein γ-tubulin and an amplification of the number of γ-tubulin foci. These effects required the centrosomal localisation mediated by the coiled-coil domain. Later in development cells expressing this truncated rassf7 protein underwent cell death. Finally, analysis of a database of tumour sequences identified a mutation in RASSF7 which would cause a similar C-terminal truncation of the protein. Based on our data this truncated protein might drive centrosomal defects and we propose the hypothesis that truncated RASSF7 could act as an oncogene in a small subset of tumours where it is mutated in this way.

Original languageEnglish
Pages (from-to)502-517
Number of pages16
JournalDevelopmental Biology
Volume409
Issue number2
Early online date10 Nov 2015
DOIs
Publication statusPublished - 15 Jan 2016

Keywords

  • Cell death
  • Centrosome
  • Mitosis
  • Oncogene
  • RASSF7
  • Xenopus

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    Gulsen, T., Hadjicosti, I., Li, Y., Zhang, X., Whitley, P. R., & Chalmers, A. D. (2016). Truncated RASSF7 promotes centrosomal defects and cell death. Developmental Biology, 409(2), 502-517. https://doi.org/10.1016/j.ydbio.2015.11.001