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Cell Growth & Differentiation Vol. 11, 455-465, August 2000
© 2000 American Association for Cancer Research

Regulated Ran-binding Protein 1 Activity Is Required for Organization and Function of the Mitotic Spindle in Mammalian Cells in Vivo1

Giulia Guarguaglini2, Luigina Renzi3, Filippo D’Ottavio, Barbara Di Fiore, Martina Casenghi2, Enrico Cundari and Patrizia Lavia4

National Research Council Centre of Evolutionary Genetics, c/o Department of Genetics and Molecular Biology, University of Rome "La Sapienza," Rome 00185, Italy

Ran-binding protein (RanBP) 1 is a major regulator of the Ran GTPase and is encoded by a regulatory target gene of E2F factors. The Ran GTPase network controls several cellular processes, including nucleocytoplasmic transport and cell cycle progression, and has recently also been shown to regulate microtubule nucleation and spindle assembly in Xenopus oocyte extracts. Here we report that RanBP1 protein levels are cell cycle regulated in mammalian cells, increase from S phase to M phase, peak in metaphase, and abruptly decline in late telophase. Overexpression of RanBP1 throughout the cell cycle yields abnormal mitoses characterized by severe defects in spindle polarization. In addition, microinjection of anti-RanBP1 antibody in mitotic cells induces mitotic delay and abnormal nuclear division, reflecting an abnormal stabilization of the mitotic spindle. Thus, regulated RanBP1 activity is required for proper execution of mitosis in somatic cells.




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