ArticleThe Journal of biological chemistry2012
The kelch protein KLHDC8B guards against mitotic errors, centrosomal amplification, and chromosomal instability.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
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- Changes in the Peripheral Blood Gene Expression Profile Induced by 3 Months of Valproate Treatment in Patients with Newly Diagnosed Epilepsy.Frontiers in neurology · 2015Article
- Reed-Sternberg cells form by abscission failure in the presence of functional Aurora B kinase.PloS one · 2015Article
- Aurora B kinase in Hodgkin lymphoma: immunohistochemical pattern of expression in neoplastic Hodgkin and Reed-Sternberg cells.Journal of molecular histology · 2014Article
- On the origin of giant cells in Hodgkin lymphoma.Communicative & integrative biology · 2014Article
- Incomplete cytokinesis and re-fusion of small mononucleated Hodgkin cells lead to giant multinucleated Reed-Sternberg cells.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Genomic Instability: The Driving Force behind Refractory/Relapsing Hodgkin's Lymphoma.Cancers · 2013Article
- Mitotic errors, aneuploidy and micronuclei in Hodgkin lymphoma pathogenesis.Communicative & integrative biology · 2013Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The malignant cell in classical Hodgkin lymphoma (HL) is the binucleated giant Reed-Sternberg cell. Chromosomal instability and mitotic errors may contribute to HL pathogenesis; one potential mitotic regulator is the kelch protein KLHDC8B, which localizes to the midbody, is expressed during mitosis, and is mutated in a subset of familial and sporadic HL. We report that disrupting KLHDC8B function in HeLa cells, B lymphoblasts, and fibroblasts leads to significant increases in multinucleation, multipolar mitoses, failed abscission, asymmetric segregation of daughter nuclei, formation of anucleated daughter cells, centrosomal amplification, and aneuploidy. We recapitulated the major pathologic features of the Reed-Sternberg cell and concluded that KLHDC8B is essential for mitotic integrity and maintenance of chromosomal stability. The significant impact of KLHDC8B implicates the central roles of mitotic regulation and chromosomal segregation in the pathogenesis of HL and provides a novel molecular mechanism for chromosomal instability in HL.
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