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The centrosome is a subcellular organelle from which a cilium assembles. Since centrosomes function as spindle poles during mitosis, they have to be present as a pair in a cell. How the correct number of centrosomes is maintained in a cell has been a major issue in the fields of cell cycle and cancer biology. Centrioles, the core of centrosomes, assemble and segregate in close connection to the cell cycle. Abnormalities in centriole numbers are attributed to decoupling from cell cycle regulation. Interestingly, supernumerary centrioles are commonly observed in cancer cells. In this review, we discuss how supernumerary centrioles are generated in diverse cellular conditions. We also discuss how the cells cope with supernumerary centrioles during the cell cycle.
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http://dx.doi.org/10.14348/molcells.2021.0220 | DOI Listing |
FEBS J
August 2025
Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX, USA.
Centrosomes play a fundamental role in nucleating and organizing microtubules in the cell and are vital for faithful chromosome segregation and maintenance of genomic stability. Loss of structural or functional integrity of centrosomes causes genomic instability and is a driver of oncogenesis. Here we identify lysine demethylase 4A (KDM4A), an epigenetic 'eraser' of chromatin methyl marks, as a centrosome-localized protein, visualized at the nanometer-scale resolution.
View Article and Find Full Text PDFIt was recently shown that inhibition of polo-like kinase 4 (PLK4) induces -dependent synthetic lethality in cancers with chromosome 17q-encoded copy number gain due to cooperative regulation of centriole duplication and mitotic spindle nucleation. We show here that chromosome 17q/TRIM37 gain is a pathognomonic feature of high-risk neuroblastoma and renders patient-derived cell lines hypersensitive to the novel PLK4 inhibitor RP-1664. We demonstrate that centriole amplification at low doses of RP-1664 contributes to this sensitivity in a - and -independent fashion.
View Article and Find Full Text PDFJ Cell Sci
July 2025
Cell and Tumour Biology , Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar Node, Navi Mumbai 410210, India.
The 14-3-3 protein family regulates several pathways in mammalian cells, including centrosome duplication. However, the precise mechanisms by which 14-3-3 paralogs regulate the centrosome cycle remain unclear. To identify the mechanisms by which 14-3-3ε regulates centrosome duplication, we altered two conserved acidic residues in the 14-3-3ε phospho-peptide-binding pocket that regulate complex formation and dissociation with the associated ligands, D127 and E134, to alanine.
View Article and Find Full Text PDFMol Biol Cell
June 2025
Department of Biological Sciences, Seoul National University, Seoul, South Korea 08826.
Many cancer cells maintain supernumerary centrioles, despite the potential risks associated with catastrophic outcomes during mitosis. In this study, we searched for cancer cell lines in which supernumerary centrioles are generated during the M phase and identified a few cell lines among the dozen examined. PLK4 activity is also required for M phase-specific generation of supernumerary centrioles.
View Article and Find Full Text PDFCytoskeleton (Hoboken)
May 2025
Cancer Biology Laboratory, Department of Bioengineering, Faculty of Engineering, Ege University, Bornova, Turkey.
Hematological and neurological expressed 1 (HN1) is homolog of Jupiter protein from Drosophila melanogaster where it functions as a microtubule-associated protein. However, in mammalian cells, HN1 is associated partially with y-tubulin in centrosomes, Stathmin for stabilizing microtubules, and Cdh1 for regulating Cyclin B1 for cell cycle regulation. Moreover, HN1 overexpression leads to early mitotic exit as well.
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