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CCDC86 is a novel Ki-67-interacting protein important for cell division
Konstantinos Stamatiou1, Aldona Chmielewska2, Shinya Ohta3
1College of Health, Medicine and Life Sciences, Department of Life Sciences, Brunel University London, London UB8 3PH, UK.
Journal of Cell Science
|January 25, 2023
Summary
CCDC86 is a novel protein in the chromosome periphery crucial for accurate cell division. Its depletion causes mitotic errors and neuroblastoma prognosis issues.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The chromosome periphery, a protein-RNA network on mitotic chromosomes, has poorly understood functions.
- New components are continually identified, yet their roles remain largely uncharacterized.
Purpose of the Study:
- To identify and characterize the function of a novel chromosome periphery-associated protein, CCDC86 (cyclon).
- To investigate CCDC86's role in mitosis and its potential as a biomarker in neuroblastoma.
Main Methods:
- RNA interference (RNAi) for CCDC86 depletion.
- Microscopy and biochemical assays to analyze cellular and molecular changes.
- Analysis of CCDC86's regulation by MYCN and its prognostic value in neuroblastoma.
Main Results:
- CCDC86 depletion led to chromosome periphery disorganization, altered localization of Ki-67 (MKI67) and nucleolin (NCL), and cytoplasmic aggregates.
- Cells lacking CCDC86 exhibited chromosome alignment errors, abnormal spindle length, increased apoptosis, and impaired kinetochore-microtubule attachments.
- CCDC86 was identified as a MYCN-regulated gene, with its expression levels correlating with neuroblastoma prognosis.
Conclusions:
- CCDC86, nucleolin (NCL), and B23 (nucleophosmin/NPM1) form subcomplexes within the chromosome periphery essential for mitotic spindle regulation and chromosome segregation.
- CCDC86 plays a critical role in maintaining mitotic fidelity.
- CCDC86 expression is a significant prognostic marker for neuroblastoma outcomes.
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