Chromosome Segregation: Evolving a Plastic Chromosome–Microtubule Interface

Navarro, Alexandra P.; Cheeseman, Iain M.

doi:10.1016/j.cub.2019.12.058

Cited by 5 publications

(5 citation statements)

References 21 publications

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“…The reduced localization of the CENP-L/N complex in mitosis suggests that this complex undergoes cell cycle–specific changes that alter its centromere localization. Based on the prevalent role of posttranslational modifications in regulating diverse aspects of kinetochore assembly and function ( Hara and Fukagawa, 2020 ; Navarro and Cheeseman, 2020 ), we hypothesized that CENP-N and CENP-L may be post translationally modified in a cell cycle–dependent manner. To test this, we isolated GFP-CENP-N from cells enriched either in mitosis or in S phase and GFP-CENP-L from mitotically enriched cells by immunoprecipitation.…”

Section: Resultsmentioning

confidence: 99%

“…Although the inner kinetochore is localized constitutively to centromeres, the structure and organization of this protein assembly changes in a cell cycle-dependent manner (Navarro and Cheeseman, 2020). First, centromeres undergo a significant structural change during G2 and upon entry into mitosis when inner kinetochore proteins CENP-C and CENP-T serve as a binding site for outer kinetochore recruitment (Cheeseman et al, 2008;Gascoigne and Cheeseman, 2013;Malvezzi et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Dynamic cell cycle–dependent phosphorylation modulates CENP-L–CENP-N centromere recruitment

Navarro

Cheeseman

2022

MBoC

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dynamic cell cycle–dependent phosphorylation modulates CENP-L–CENP-N centromere recruitment

Navarro

Cheeseman

2022

MBoC

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“…This means that the assembly of CCAN is dependent on the interactions of these protein complexes. 16 contacts for ongoing reconfiguration at various cell cycle stages [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical implications and immune features of CENPN in breast cancer

Gui,

Tian,

et al. 2023

BMC Cancer

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Background A number of human diseases have been associated with Centromere protein N (CENPN), but its role in breast cancer is unclear. Methods A pan-cancer database of Genotype Tissue Expression (GTEx) and the Cancer Genome Atlas (TCGA) were used to examine the expression of CENPN. Using TCGA clinical survival data and breast cancer specimens from our center for validation, the relationship between CENPN expression, breast cancer prognosis, and clinicopathological characteristics of patients was examined. Bioinformatics was utilized to conduct an enrichment study of CENPN. Additionally, the potential of CENPN as a predictive biomarker for immunotherapy success was confirmed by analyzing the co-expression of CENPN with immune-checkpoint related genes, reviewing the TCGA database, and evaluating the correlation between CENPN expression and immune cell infiltration. Using the CCK8 test and colony formation assay, CENPN was evaluated for its ability to inhibit breast cancer cell proliferation. Transwell assays and scratch tests were used to assess the impact of CENPN on breast cancer cell migration. Results CENPN is found in a wide range of tumors, including breast cancer. Additional investigation revealed that CENPN was co-expressed with the majority of immune checkpoint-related genes, had the potential to serve as a predictive biomarker for immunotherapy effectiveness, and that high CENPN expression was linked to high Tregs and low CD8 + T cells and NK cells. Breast cancer cells' malignant characteristics, such as migration and cell proliferation, were inhibited by CENPN knockdown. Conclusions According to our findings, CENPN may be an oncogene in breast cancer, as well as a new therapeutic target for immune checkpoint inhibitors.

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“…This altered localization of the CENP-L/N complex in mitosis suggests that this complex undergoes cell cycle specific changes that alter its centromere localization. Based on the prevalence of post-translational modifications in regulating diverse aspects of kinetochore assembly and function (Hara and Fukagawa, 2020;Navarro and Cheeseman, 2020), we hypothesized that CENP-N and CENP-L might be post-translationally modified in a cell cycledependent manner. To test this, we isolated GFP-CENP-N from cells enriched in either mitosis or in S phase and GFP-CENP-L from mitotically enriched cells using immuno-precipitation.…”

Section: Cenp-l and Cenp-n Are Phosphorylated In Mitosismentioning

confidence: 99%

Dynamic cell cycle-dependent phosphorylation modulates CENP-L-CENP-N centromere recruitment

Navarro

Cheeseman

2021

Preprint

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The kinetochore is a macromolecular structure that is required to ensure proper chromosome segregation during each cell division. The kinetochore is assembled upon a platform of the 16-subunit Constitutive Centromere Associated Network (CCAN), which is present at centromeres throughout the cell cycle. The nature and regulation of CCAN assembly, interactions, and dynamics required to facilitate changing centromere properties and requirements remain to be fully elucidated. The CENP-LN CCAN sub-complex displays a unique cell cycle-dependent localization behavior, peaking in S phase. Here, we demonstrate that phosphorylation of CENP-L and CENP-N controls CENP-LN complex formation and localization in a cell cycle-dependent manner. Mimicking constitutive phosphorylation of either CENP-L or CENP-N or simultaneously preventing phosphorylation of both proteins prevents CENP-LN localization and disrupts chromosome segregation. Together, our work suggests that cycles of phosphorylation and dephosphorylation are critical for CENP-LN complex recruitment and dynamics at centromeres to enable cell cycle-dependent CCAN reorganization.

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Chromosome Segregation: Evolving a Plastic Chromosome–Microtubule Interface

Cited by 5 publications

References 21 publications

Dynamic cell cycle–dependent phosphorylation modulates CENP-L–CENP-N centromere recruitment

Dynamic cell cycle–dependent phosphorylation modulates CENP-L–CENP-N centromere recruitment

Clinical implications and immune features of CENPN in breast cancer

Dynamic cell cycle-dependent phosphorylation modulates CENP-L-CENP-N centromere recruitment

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