Fish lineage-specific gene, [Siaz-interacting nuclear protein], modulates neural plate formation in embryogenesis and shares homology with human TPX2 protein, a member of the vertebrate mitogen-activating protein family. In spite of the presence of the TPX2 domain in Sinup, its cellular function has been unknown. As an initial approach to this question, we expressed Sinup by injecting mRNAs into zebrafish embryos at the one- to two-cell stage. First of all, Sinup-EGFP was associated with centrosomes and mitotic spindles. In particular, Sinup was localized to the spindle poles and midbody microtubules during the period between anaphase and cytokinesis. Second, various deleted mutants of Sinup-EGFP failed to be associated with the centrosomes and mitotic spindles. Third, a Sinup mutant, where the 144th Serine residue was converted to alanine, not only disturbed the mitotic spindle organization, such as multipolar spindles, fragmented spindle poles, and flattened spindles, but also arrested the cell cycle at metaphase and cell movement. Finally, Sinup is phosphorylated by Aurora A and the 144th Serine mutant of Sinup is partially phosphorylated by Aurora A kinase. We thus propose that Sinup is an essential element for the integrity of centrosomes and mitotic spindle fibers as well as for the normal process of cell cycle and cellular movement in vertebrate embryos.
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http://dx.doi.org/10.1080/19768354.2017.1308438 | DOI Listing |
Nat Commun
January 2025
Instituto de Biología Funcional y Genómica, Zacarías González 2, Salamanca, 37007, Spain.
Accurate gametogenesis requires the establishment of the telomere bouquet, an evolutionarily conserved, 3D chromosomal arrangement. In this spatial configuration, telomeres temporarily aggregate at the nuclear envelope during meiotic prophase, which facilitates chromosome pairing and recombination. The mechanisms governing the assembly of the telomere bouquet remain largely unexplored, primarily due to the challenges in visualizing and manipulating the bouquet.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Healthand, Department of Frontiers Science Center for Disease-related Molecular Network, Core Facilities, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. Electronic address:
NEK2, a serine/threonine protein kinase, is integral to mitotic events such as centrosome duplication and separation, microtubule stabilization, spindle assembly checkpoint, and kinetochore attachment. However, NEK2 overexpression leads to centrosome amplification and chromosomal instability, which are significantly associated with various malignancies, including liver, breast, and non-small cell lung cancer. This overexpression could facilitate tumor development and confer resistance to therapy by promoting aberrant cell division and centrosome amplification.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA. Electronic address:
Selective inhibitors that target cyclin dependent kinases 4 and 6 (CDK4/6i) are FDA approved for treatment of a subset of breast cancers and are being evaluated in numerous clinical trials for other cancers. Despite this advance, a subset of tumors are intrinsically resistant to these drugs and acquired resistance is nearly inevitable. Recent mechanistic evidence suggests that in addition to stalling the cell cycle, the anti-tumor effects of CDK4/6i involve the induction of chromosomal instability (CIN).
View Article and Find Full Text PDFEMBO Rep
January 2025
Cellular and Molecular Physiology, Institute of Systems Molecular and Integrative Biology, University of Liverpool, Crown St, Liverpool, L69 3BX, UK.
Cancer cells often display centrosome amplification, requiring the kinesin KIFC1/HSET for centrosome clustering to prevent multipolar spindles and cell death. In parallel siRNA screens of deubiquitinase enzymes, we identify OTUD6B as a positive regulator of KIFC1 expression that is required for centrosome clustering in triple-negative breast cancer (TNBC) cells. OTUD6B can localise to centrosomes and the mitotic spindle and interacts with KIFC1.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Life Science and Medical Bioscience, Laboratory of Cytoskeletal Logistics, Graduate School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo, Japan.
In mammalian epithelial cells, cytoplasmic microtubules are mainly non-centrosomal, through the functions of the minus-end binding proteins CAMSAP2 and CAMSAP3. When cells enter mitosis, cytoplasmic microtubules are reorganized into the spindle composed of both centrosomal and non-centrosomal microtubules. The function of the CAMSAP proteins upon spindle assembly remains unknown, as these do not exhibit evident localization to spindle microtubules.
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