ArticleCell cycle (Georgetown, Tex.)2015
Therapeutic potential of mitotic interaction between the nucleoporin Tpr and aurora kinase A.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Unraveling dynamics of nuclear pore and chromatin via HS-AFM.Anatomical science international · 2026Review
- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- Review
- ZC3HC1 has many functions distinct from TPR and is dispensable for TPR localisation to the nuclear basket.Wellcome open research · 2025Article
- The Expression Regulation and Cancer-Promoting Roles of RACGAP1.Biomolecules · 2024Review
- Ethanolic Extract of Red Okra Pods Induces Aberrant Spindle Segregation and Apoptotic Cell Death by Disrupting the Wnt Signaling Pathway in Colon Cancer Cells.Iranian journal of medical sciences · 2024Article
- Advances in the understanding of nuclear pore complexes in human diseases.Journal of cancer research and clinical oncology · 2024Review
- CircZCCHC2 decreases pirarubicin sensitivity and promotes triple-negative breast cancer development via the miR-1200/TPR axis.iScience · 2024Article
- Article
- Article
- Aurora-A kinase is differentially expressed in the nucleus and cytoplasm in normal Müllerian epithelium and benign, borderline and malignant serous ovarian neoplasms.Diagnostic pathology · 2021Article
- Autocrine GMCSF Signaling Contributes to Growth of HER2Cancer research · 2021Article
- New Activities of the Nuclear Pore Complexes.Cells · 2021Article
- Article
- Article
- RACK1 affects the progress of G2/M by regulating Aurora-A.Cell cycle (Georgetown, Tex.) · 2019Article
- Nucleoporin Nup58 localizes to centrosomes and mid-bodies during mitosis.Cell division · 2019Article
- Colorectal cancer cells require glycogen synthase kinase-3β for sustaining mitosis via translocated promoter region (TPR)-dynein interaction.Oncotarget · 2018Article
- Impact of Nucleoporin-Mediated Chromatin Localization and Nuclear Architecture on HIV Integration Site Selection.Journal of virology · 2015Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spindle poles are defined by centrosomes; therefore, an abnormal number or defective structural organization of centrosomes can lead to loss of spindle bipolarity and genetic integrity. Previously, we showed that Tpr (translocated promoter region), a component of the nuclear pore complex (NPC), interacts with Mad1 and dynein to promote proper chromosome segregation during mitosis. Tpr also associates with p53 to induce autophagy. Here, we report that Tpr depletion induces mitotic catastrophe and enhances the rate of tetraploidy and polyploidy. Mechanistically, Tpr interacts, via its central domain, with Aurora A but not Aurora B kinase. In Tpr-depleted cells, the expression levels, centrosomal localization and phosphorylation of Aurora A were all reduced. Surprisingly, an Aurora A inhibitor, Alisertib (MLN8237), also disrupted centrosomal localization of Tpr and induced mitotic catastrophe and cell death in a time- and dose-dependent manner. Strikingly, over-expression of Aurora A disrupted Tpr centrosomal localization only in cells with supernumerary centrosomes but not in bipolar cells. Our results highlight the mutual regulation between Tpr and Aurora A and further confirm the importance of nucleoporin function in spindle pole organization, bipolar spindle assembly, and mitosis; functions that are beyond the conventional nucleocytoplasmic transport and NPC structural roles of nucleoporins. Furthermore, the central coiled-coil domain of Tpr binds to and sequesters extra Aurora A to safeguard bipolarity. This Tpr domain merits further investigation for its ability to inhibit Aurora kinase and as a potential therapeutic agent in cancer treatment.
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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.