RASSF7 is a member of a new family of RAS association domain- containing proteins and is required for completing mitosis

Victoria Sherwood, Ria Manbodh, Carol Sheppard, Andrew D Chalmers

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Abstract

Mitosis is a fundamental feature of all cellular organisms. It must be tightly regulated to allow normal tissue growth and to prevent cancer formation. Here, we identify a new protein that is required for mitosis. We show that the Ras association (RA) domain containing protein, RASSF7, is part of an evolutionarily conserved group of four RA domain containing proteins. These are RASSF7, RASSF8 and two new RASSF proteins P-CIP1/RASSF9 and RASSF10. We call this group the N-terminal RASSF family. We analysed the function of Xenopus RASSF7. RASSF7 was found to be expressed in several embryonic tissues including the skin, eyes and neural tube. Knocking down its function led to cells failing to form a mitotic spindle and arresting in mitosis. This caused nuclear breakdown, apoptosis and a striking loss of tissue architecture in the neural tube. Consistent with a role in spindle formation, RASSF7 protein was found to localise to the centrosome. This localisation occurred in a microtubule-dependent manner, demonstrating that there is a mutually dependant relationship between RASSF7 localisation and spindle formation. Thus RASSF7, the first member of the N-terminal RASSF family to be functionally analysed, is a centrosome-associated protein which is required to form a spindle and complete mitosis in the neural tube.
Original languageEnglish
Pages (from-to)1772-1782
Number of pages11
JournalMolecular Biology of the Cell
Volume19
Issue number4
Early online date13 Feb 2008
DOIs
Publication statusPublished - 1 Apr 2008

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