Re-evaluating the role of Tao1 in the spindle checkpoint

Westhorpe, Frederick G.; Diez, Maria; Gurden, Mark D.; Tighe, Anthony; Taylor, Stephen S.

doi:10.1007/s00412-010-0261-1

Cited by 33 publications

(32 citation statements)

References 43 publications

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“…4A). Our siRNAs did not have off-target effects on the SAC protein Mad2 (Hubner et al 2010;Westhorpe et al 2010) because the intracellular Mad2 levels remained constant after siRNA treatment (Supple- mental Fig. 5A).…”

Section: Resultsmentioning

confidence: 91%

A conserved role for COMA/CENP-H/I/N kinetochore proteins in the spindle checkpoint

Matson¹,

Demirel²,

Stukenberg³

et al. 2012

Genes Dev.

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The COMA/CENP-H/I kinetochore complex regulates microtubule dynamics at kinetochores. The complex is also required to generate spindle checkpoint signals in both yeast and human cells under conditions where Aurora B activity is compromised. Our data explain why mammalian cells treated with Aurora inhibitors still have a functional spindle assembly checkpoint (SAC), since the checkpoint signals through CENP-H/I/N. The SAC effect from depleting the CENP-H/I/N complex cannot be explained by a weakened SAC signal, and the complex has no role in the SAC response to paclitaxel. We propose a model to explain the differential response of human cells to nocodazole and paclitaxel.

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Section: Resultsmentioning

confidence: 91%

A conserved role for COMA/CENP-H/I/N kinetochore proteins in the spindle checkpoint

Matson¹,

Demirel²,

Stukenberg³

et al. 2012

Genes Dev.

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“…2G). Although MAD2 is a frequent siRNA offtarget (Hübner et al, 2010;Sigoillot et al, 2012;Westhorpe et al, 2010), the expression of MAD2, MAD1, BUB1 and BUB3 remained unchanged after TRAIP KD (supplementary material Fig. S1B,C).…”

Section: Traip Regulates Progression Through Early Phases Of Mitosismentioning

confidence: 94%

The TRAF-interacting protein (TRAIP) is a regulator of the spindle assembly checkpoint

Chapard¹,

Meraldi²,

Gleich³

et al. 2014

Journal of Cell Science

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Accurate chromosome segregation during mitosis is temporally and spatially coordinated by fidelity-monitoring checkpoint systems. Deficiencies in these checkpoint systems can lead to chromosome segregation errors and aneuploidy, and promote tumorigenesis. Here, we report that the TRAF-interacting protein (TRAIP), a ubiquitously expressed nucleolar E3 ubiquitin ligase important for cellular proliferation, is localized close to mitotic chromosomes. Its knockdown in HeLa cells by RNA interference (RNAi) decreased the time of early mitosis progression from nuclear envelope breakdown (NEB) to anaphase onset and increased the percentages of chromosome alignment defects in metaphase and lagging chromosomes in anaphase compared with those of control cells. The decrease in progression time was corrected by the expression of wild-type but not a ubiquitin-ligase-deficient form of TRAIP. TRAIP-depleted cells bypassed taxol-induced mitotic arrest and displayed significantly reduced kinetochore levels of MAD2 (also known as MAD2L1) but not of other spindle checkpoint proteins in the presence of nocodazole. These results imply that TRAIP regulates the spindle assembly checkpoint, MAD2 abundance at kinetochores and the accurate cellular distribution of chromosomes. The TRAIP ubiquitin ligase activity is functionally required for the spindle assembly checkpoint control.

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“…Stable HeLa cell lines were generated using Flp-FRT-mediated recombination (Tighe et al, 2004). Cells were synchronised in S-phase as described (Westhorpe et al, 2010).…”

Section: Cell Linesmentioning

confidence: 99%

p31comet-mediated extraction of Mad2 from the MCC promotes efficient mitotic exit

Westhorpe

Tighe

Lara-González

et al. 2011

Journal of Cell Science

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119

163

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SummaryAccurate chromosome segregation requires the spindle assembly checkpoint to be active at the onset of mitosis, before being silenced following chromosome alignment. p31 comet is a checkpoint antagonist in that its inhibition delays mitotic exit, whereas its overexpression overrides the checkpoint. How exactly p31 comet antagonises the checkpoint is unclear. A prevalent model is that p31 comet acts as a 'cap' by inhibiting recruitment of the open conformation form of Mad2 (O-Mad2) to the kinetochore-bound complex of Mad1-C-Mad2 (closed conformation Mad2), an essential step that is required for checkpoint activation. Here, we show that although p31 comet localises to kinetochores in mitosis, modulation of its activity has no effect on recruitment of O-Mad2 to kinetochores. Rather, our observations support a checkpoint-silencing role for p31 comet downstream of kinetochores. We show that p31 comet binds Mad2 when it is bound to the mitotic checkpoint complex (MCC) components BubR1 and Cdc20. Furthermore, RNAi-mediated inhibition of p31 comet results in more Mad2 bound to BubR1-Cdc20, and conversely, overexpression of p31 comet results in less Mad2 bound to BubR1-Cdc20. Addition of recombinant p31 comet to checkpoint-arrested extracts removes Mad2 from the MCC, whereas a p31 comet mutant that cannot bind Mad2 has no effect. Significantly, expression of a Mad2 mutant that cannot bind p31 comet prolongs the metaphase to anaphase transition. Taken together, our data support the notion that p31 comet negatively regulates the spindle assembly checkpoint by extracting Mad2 from the MCC.

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Re-evaluating the role of Tao1 in the spindle checkpoint

Cited by 33 publications

References 43 publications

A conserved role for COMA/CENP-H/I/N kinetochore proteins in the spindle checkpoint

A conserved role for COMA/CENP-H/I/N kinetochore proteins in the spindle checkpoint

The TRAF-interacting protein (TRAIP) is a regulator of the spindle assembly checkpoint

p31comet-mediated extraction of Mad2 from the MCC promotes efficient mitotic exit

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