Supernumerary centrioles are frequently observed in diverse types of cancer cells. In this study, we investigated the mechanism underlying the generation of supernumerary centrioles during the M phase. We generated the triple knockout (KO) cells and determined the configurations of the centriole during the cell cycle. The triple KO cells exhibited a precocious separation of centrioles and unscheduled centriole assembly in the M phase. Supernumerary centrioles in the triple KO cells were present throughout the cell cycle; however, among all the centrioles, only two maintained an intact composition, including CEP135, CEP192, CEP295 and CEP152. Intact centrioles were formed during the S phase and the rest of the centrioles may be generated during the M phase. M-phase-assembled centrioles lacked the ability to organize microtubules in the interphase; however, a fraction of them may acquire pericentriolar material to organize microtubules during the M phase. Taken together, our work reveals the heterogeneity of the supernumerary centrioles in the triple KO cells. .
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http://dx.doi.org/10.1080/15384101.2021.1950386 | DOI Listing |
Cytoskeleton (Hoboken)
September 2024
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.
View Article and Find Full Text PDFCancer Biol Ther
December 2023
Molecular Pharmacology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Cyclin-dependent Kinase 2 (CDK2) inhibition prevents supernumerary centrosome clustering. This causes multipolarity, anaphase catastrophe and apoptotic death of aneuploid cancers. This study elucidated how CDK2 antagonism affected centrosome stoichiometry.
View Article and Find Full Text PDFJ Cell Biol
December 2023
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Polo-like kinase 4 (PLK4) is a key regulator of centriole biogenesis, but how PLK4 selects a single site for procentriole assembly remains unclear. Using ultrastructure expansion microscopy, we show that PLK4 localizes to discrete sites along the wall of parent centrioles. While there is variation in the number of sites PLK4 occupies on the parent centriole, most PLK4 localize at a dominant site that directs procentriole assembly.
View Article and Find Full Text PDFAnn Hum Genet
January 2024
Division of Molecular Medicine, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
Most mammalian cells have a single primary cilium that acts as a signalling hub in mediating cellular functions. However, little is known about the mechanisms that result in aberrant supernumerary primary cilia per cell. In this study, we re-analysed a previously published whole-genome siRNA-based reverse genetic screen for genes mediating ciliogenesis to identify knockdowns that permit multi-ciliation.
View Article and Find Full Text PDFEMBO J
October 2023
Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
Unscheduled increases in ploidy underlie defects in tissue function, premature aging, and malignancy. A concomitant event to polyploidization is the amplification of centrosomes, the main microtubule organization centers in animal cells. Supernumerary centrosomes are frequent in tumors, correlating with higher aggressiveness and poor prognosis.
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