Human RASSF7 regulates the microtubule cytoskeleton and is required for spindle formation, Aurora B activation and chromosomal congression during mitosis.
RASSF7, a member of the N-terminal Ras association domain family, has increased expression in various cancers and, on the basis of our previous work in Xenopus embryos, may be a regulator of mitosis. In the present study, we address, for the first time, the role of human RASSF7 in mitosis. We demonstrate that RASSF7 is expressed in a broad range of different cell types and that this expression could be enhanced following exposure to hypoxia. Knocking down RASSF7 in human cell lines inhibited cell growth and induced defects in mitosis, including aberrant spindle formation and a failure in chromosomal congression. In order to understand the molecular basis of the defects in more detail, we analysed the activity of mitotic signalling proteins and found that activation of Aurora B did not occur in cells in which RASSF7 was knocked down. We also show that endogenous RASSF7 protein localizes to the centrosome and demonstrate using microtubule-regrowth assays that RASSF7 is an important regulator of microtubule dynamics. On the basis of these observations, we propose that, owing to its key role in regulating the microtubule cytoskeleton, RASSF7 is required for mitosis in human cells.
Recino
Asha
A
Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath, UK.
Sherwood
Victoria
V
Flaxman
Amy
A
Cooper
Wendy N
WN
Latif
Farida
F
Ward
Andrew
A
Chalmers
Andrew D
AD
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism; D020090:Chromosome Segregation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C092941:RASSF7 protein, human; D014157:Transcription Factors; C576921:AURKB protein, human; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases