ArticlePLoS genetics2015
Aurora-A-Dependent Control of TACC3 Influences the Rate of Mitotic Spindle Assembly.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 54 citations in OpenAlex.
- Activator mimicry by PP6 regulatory subunits directs Aurora A dephosphorylation in mitosis.The EMBO journal · 2026Article
- Mechanistic design of cell-penetrating disruptors for phospho-dependent TACC3-CHC interaction.Structure (London, England : 1993) · 2026Article
- The γ-TuRC: mastermind of multipurpose actions at the centrosome.Cellular and molecular life sciences : CMLS · 2026Review
- Centrioles generate two scaffolds with distinct biophysical properties to build mitotic centrosomes.Science advances · 2025Article
- CEP192 localises mitotic Aurora-A activity by priming its interaction with TPX2.The EMBO journal · 2024Article
- Article
- PAK1-Dependent Regulation of Microtubule Organization and Spindle Migration Is Essential for the Metaphase I-Metaphase II Transition in Porcine Oocytes.Biomolecules · 2024Article
- The GCN2/eIF2αK stress kinase regulates PP1 to ensure mitotic fidelity.EMBO reports · 2023Article
- Article
- PAK1 Is Involved in the Spindle Assembly during the First Meiotic Division in Porcine Oocytes.International journal of molecular sciences · 2023Article
- Insights Into Mechanisms of Oriented Division From Studies in 3D Cellular Models.Frontiers in cell and developmental biology · 2022Review
- Overlapping roles for PLK1 and Aurora A during meiotic centrosome biogenesis in mouse spermatocytes.EMBO reports · 2021Article
- CRISPR/Cas9 screening identifies a kinetochore-microtubule dependent mechanism for Aurora-A inhibitor resistance in breast cancer.Cancer communications (London, England) · 2021Article
- Phospho-regulation of mitotic spindle assembly.Cytoskeleton (Hoboken, N.J.) · 2020Review
- AURKA destruction is decoupled from its activity at mitotic exit but is essential to suppress interphase activity.Journal of cell science · 2020Article
- Clathrin's adaptor interaction sites are repurposed to stabilize microtubules during mitosis.The Journal of cell biology · 2020Article
- Article
- Covalent Aurora A regulation by the metabolic integrator coenzyme A.Redox biology · 2020Article
- Potential involvement of RITA in the activation of Aurora A at spindle poles during mitosis.Oncogene · 2019Article
- The microtubule-associated protein HURP recruits the centrosomal protein TACC3 to regulate K-fiber formation and support chromosome congression.The Journal of biological chemistry · 2018Article
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
The essential mammalian gene TACC3 is frequently mutated and amplified in cancers and its fusion products exhibit oncogenic activity in glioblastomas. TACC3 functions in mitotic spindle assembly and chromosome segregation. In particular, phosphorylation on S558 by the mitotic kinase, Aurora-A, promotes spindle recruitment of TACC3 and triggers the formation of a complex with ch-TOG-clathrin that crosslinks and stabilises kinetochore microtubules. Here we map the Aurora-A-binding interface in TACC3 and show that TACC3 potently activates Aurora-A through a domain centered on F525. Vertebrate cells carrying homozygous F525A mutation in the endogenous TACC3 loci exhibit defects in TACC3 function, namely perturbed localization, reduced phosphorylation and weakened interaction with clathrin. The most striking feature of the F525A cells however is a marked shortening of mitosis, at least in part due to rapid spindle assembly. F525A cells do not exhibit chromosome missegregation, indicating that they undergo fast yet apparently faithful mitosis. By contrast, mutating the phosphorylation site S558 to alanine in TACC3 causes aneuploidy without a significant change in mitotic duration. Our work has therefore defined a regulatory role for the Aurora-A-TACC3 interaction beyond the act of phosphorylation at S558. We propose that the regulatory relationship between Aurora-A and TACC3 enables the transition from the microtubule-polymerase activity of TACC3-ch-TOG to the microtubule-crosslinking activity of TACC3-ch-TOG-clathrin complexes as mitosis progresses. Aurora-A-dependent control of TACC3 could determine the balance between these activities, thereby influencing not only spindle length and stability but also the speed of spindle formation with vital consequences for chromosome alignment and segregation.
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