RINGO C is required to sustain the spindle-assembly checkpoint.

Abstract:

:RINGO/Speedy proteins are direct activators of Cdk1 and Cdk2 that have no sequence homology to cyclins. We have characterized the role in cell-cycle progression of a new human member of this protein family referred to as RINGO C. We show that siRNA-mediated knockdown of RINGO C results in premature mitotic exit with misaligned chromosomes, even in the presence of microtubule poisons. Time-lapse-microscopy experiments suggest that RINGO C is involved in the spindle-assembly checkpoint (SAC). Consistent with this idea, RINGO-C-depleted cells show impaired recruitment of the SAC components Mad2, Bub1 and BubR1. As the checkpoint is overridden, cells display defective chromosome segregation, which leads to an increased number of micronuclei and binucleated structures. Intriguingly, we found that RINGO C can associate with the mitotic kinase Aurora B, and downregulation of RINGO C produces mislocalization of the active form of Aurora B in prometaphase. Taken together, our results indicate a role for RINGO C in the mitotic checkpoint, which might be mediated by defective recruitment of SAC components and deregulation of the activity of Aurora kinase B.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Mourón S,de Cárcer G,Seco E,Fernández-Miranda G,Malumbres M,Nebreda AR

doi

10.1242/jcs.059964

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

2586-95

issue

Pt 15

eissn

0021-9533

issn

1477-9137

pii

jcs.059964

journal_volume

123

pub_type

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