ArticleThe Journal of cell biology2023
PP6 regulation of Aurora A-TPX2 limits NDC80 phosphorylation and mitotic spindle size.
Article in The Journal of cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
- Structure and function of the outer kinetochore.Nature reviews. Molecular cell biology · 2026Review
- Article
- A chromatin-associated pool of Aurora A controls kinetochore-microtubule attachments to ensure chromosome biorientation.Science advances · 2026Article
- A murine cytomegalovirus cell cycle regulator (m54.5p) evolved within the conserved viral DNA polymerase gene.PLoS pathogens · 2026Article
- Developmental regulation of kinetochore phosphorylation determines mitotic fidelity.bioRxiv : the preprint server for biology · 2026Article
- AURKA-mediated destabilization of SAPS3 drives ferroptosis evasion via 7-dehydrocholesterol biosynthesis in colorectal cancer.Cell death & disease · 2026Article
- A chromatin-associated pool of Aurora A controls kinetochore-microtubule attachments to ensure chromosome biorientation.bioRxiv : the preprint server for biology · 2025Article
- Dynamic phosphorylation of MIS12 ensures accurate kinetochore-microtubule attachment by expanding the fibrous corona.Molecular biology of the cell · 2025Article
- Loss of Fbxo45 in AT2 cells leads to insufficient histone supply and initiates lung adenocarcinoma.Cell death and differentiation · 2025Article
- Insights into the role of phosphorylation on microtubule cross-linking by PRC1.Molecular biology of the cell · 2025Article
- An Aurora kinase A-BOD1L1-PP2A B56 axis promotes chromosome segregation fidelity.Cell reports · 2025Article
- The multifaceted functions of SPC25 in cancer: from molecular pathways to targeted therapy.Frontiers in medicine · 2025Review
- CEP192 localises mitotic Aurora-A activity by priming its interaction with TPX2.The EMBO journal · 2024Article
- Review
- Centrosome age breaks spindle size symmetry even in cells thought to divide symmetrically.The Journal of cell biology · 2024Article
- An Aurora kinase A-BOD1L1-PP2A B56 Axis promotes chromosome segregation fidelity.bioRxiv : the preprint server for biology · 2024Article
- Inducible protein degradation as a strategy to identify Phosphoprotein Phosphatase 6 substrates in RAS-mutant colorectal cancer cells.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Amplification of the mitotic kinase Aurora A or loss of its regulator protein phosphatase 6 (PP6) have emerged as drivers of genome instability. Cells lacking PPP6C, the catalytic subunit of PP6, have amplified Aurora A activity, and as we show here, enlarged mitotic spindles which fail to hold chromosomes tightly together in anaphase, causing defective nuclear structure. Using functional genomics to shed light on the processes underpinning these changes, we discover synthetic lethality between PPP6C and the kinetochore protein NDC80. We find that NDC80 is phosphorylated on multiple N-terminal sites during spindle formation by Aurora A-TPX2, exclusively at checkpoint-silenced, microtubule-attached kinetochores. NDC80 phosphorylation persists until spindle disassembly in telophase, is increased in PPP6C knockout cells, and is Aurora B-independent. An Aurora-phosphorylation-deficient NDC80-9A mutant reduces spindle size and suppresses defective nuclear structure in PPP6C knockout cells. In regulating NDC80 phosphorylation by Aurora A-TPX2, PP6 plays an important role in mitotic spindle formation and size control and thus the fidelity of cell division.
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Registered trials
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 Socratic graph.