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Truncated RASSF7 promotes centrosomal defects and cell death

Gulsen, T; Hadjicosti, I; Li, Y; Zhang, X; Whitley, PR; Chalmers, AD; (2016) Truncated RASSF7 promotes centrosomal defects and cell death. Developmental Biology , 409 (2) pp. 502-517. 10.1016/j.ydbio.2015.11.001. Green open access

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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.

Type: Article
Title: Truncated RASSF7 promotes centrosomal defects and cell death
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ydbio.2015.11.001
Publisher version: https://doi.org/10.1016/j.ydbio.2015.11.001
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: RASSF7; Centrosome; Mitosis; Oncogene; Xenopus; Cell death
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1532443
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