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TD-60 (also known as RCC2) is a highly conserved protein that structurally resembles the Ran guanine exchange factor (GEF) RCC1, but has not previously been shown to have GEF activity. TD-60 has a typical chromosomal passenger complex (CPC) distribution in mitotic cells, but associates with integrin complexes and is involved in cell motility during interphase. Here we show that TD-60 exhibits GEF activity, in vitro and in cells, for the small GTPase RalA. TD-60 or RalA depletion causes spindle abnormalities in prometaphase associated with abnormal centromeric accumulation of CPC components. TD-60 and RalA apparently work together to contribute to the regulation of kinetochore-microtubule interactions in early mitosis. Importantly, several mitotic phenotypes caused by TD-60 depletion are reverted by the expression of a GTP-locked mutant, RalA (Q72L). The demonstration that a small GTPase participates in the regulation of the CPC reveals a level of mitotic regulation not suspected in previous studies.

Original publication

DOI

10.1038/ncomms8678

Type

Journal article

Journal

Nat Commun

Publication Date

09/07/2015

Volume

6

Keywords

Aurora Kinase B, Cell Cycle Proteins, Cell Line, Tumor, Cell Movement, Centromere, Chromosomal Proteins, Non-Histone, Chromosome Segregation, Guanine Nucleotide Exchange Factors, HeLa Cells, Humans, In Vitro Techniques, Inhibitor of Apoptosis Proteins, Mitosis, Prometaphase, Spindle Apparatus, ral GTP-Binding Proteins