ArticlePloS one2013
Tripolin A, a novel small-molecule inhibitor of aurora A kinase, reveals new regulation of HURP's distribution on microtubules.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 19 citations in OpenAlex.
- Research progress on the relationship between AURKA and tumorigenesis: the neglected nuclear function of AURKA.Annals of medicine · 2024Review
- HURP localization in metaphase is the result of a multi-step process requiring its phosphorylation at Ser627 residue.Frontiers in cell and developmental biology · 2023Article
- The role of Aurora-A in human cancers and future therapeutics.American journal of cancer research · 2020Review
- Discovery of thalicthuberine as a novel antimitotic agent from nature that disrupts microtubule dynamics and induces apoptosis in prostate cancer cells.Cell cycle (Georgetown, Tex.) · 2018Article
- Mechanisms of Chromosome Congression during Mitosis.Biology · 2017Review
- Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes.The Journal of cell biology · 2015Article
- Aurora-A-Dependent Control of TACC3 Influences the Rate of Mitotic Spindle Assembly.PLoS genetics · 2015Article
- Therapeutic potential of mitotic interaction between the nucleoporin Tpr and aurora kinase A.Cell cycle (Georgetown, Tex.) · 2015Article
- Mitotic spindle multipolarity without centrosome amplification.Nature cell biology · 2014Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitotic regulators exhibiting gain of function in tumor cells are considered useful cancer therapeutic targets for the development of small-molecule inhibitors. The human Aurora kinases are a family of such targets. In this study, from a panel of 105 potential small-molecule inhibitors, two compounds Tripolin A and Tripolin B, inhibited Aurora A kinase activity in vitro. In human cells however, only Tripolin A acted as an Aurora A inhibitor. We combined in vitro, in vivo single cell and in silico studies to demonstrate the biological action of Tripolin A, a non-ATP competitive inhibitor. Tripolin A reduced the localization of pAurora A on spindle microtubules (MTs), affected centrosome integrity, spindle formation and length, as well as MT dynamics in interphase, consistent with Aurora A inhibition by RNAi or other specific inhibitors, such as MLN8054 or MLN8237. Interestingly, Tripolin A affected the gradient distribution towards the chromosomes, but not the MT binding of HURP (Hepatoma Up-Regulated Protein), a MT-associated protein (MAP) and substrate of the Aurora A kinase. Therefore Tripolin A reveals a new way of regulating mitotic MT stabilizers through Aurora A phosphorylation. Tripolin A is predicted to bind Aurora A similarly but not identical to MLN8054, therefore it could be used to dissect pathways orchestrated by Aurora kinases as well as a scaffold for further inhibitor development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.