We have identified a unique human microtubule-associated protein (MAP) named ASAP for ASter-Associated Protein. ASAP localizes to microtubules in interphase, associates with the mitotic spindle during mitosis, localizes to the central body during cytokinesis and directly binds to purified microtubules by its COOH-terminal domain. Overexpression of ASAP induces profound bundling of cytoplasmic microtubules in interphase cells and aberrant monopolar spindles in mitosis. Depletion of ASAP by RNA interference results in severe mitotic defects: it provokes aberrant mitotic spindle, delays mitotic progression, and leads to defective cytokinesis or cell death. These results suggest a crucial role for ASAP in the organization of the bipolar mitotic spindle, mitosis progression, and cytokinesis and define ASAP as a key factor for proper spindle assembly.
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http://dx.doi.org/10.1073/pnas.0500964102 | DOI Listing |
Int J Mol Sci
December 2024
Departamento de Biologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14040-901, SP, Brazil.
In the flower development study, we identified SCI1 (Stigma/style Cell-cycle Inhibitor 1), a regulator of cell proliferation. SCI1 interacts with NtCDKG;2 ( Cyclin-Dependent Kinase G;2), a homolog of human CDK11, which is responsible for RanGTP-dependent microtubule stabilization, regulating spindle assembly rate. In a Y2H screening of a cDNA library using NtCDKG;2 as bait, a RanBP1 (Ran-Binding Protein 1) was revealed as its interaction partner.
View Article and Find Full Text PDFCurr Biol
January 2025
Department of Cell Biology, Duke University Medical Center, Durham, NC 27705, USA; Duke Center for Quantitative Living Systems, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:
Anaphase is tightly controlled spatiotemporally to ensure proper separation of chromosomes. The mitotic spindle, the self-organized microtubule structure driving chromosome segregation, scales in size with the available cytoplasm. Yet, the relationship between spindle size and chromosome movement remains poorly understood.
View Article and Find Full Text PDFCytotechnology
February 2025
Department of Pharmacology and Toxicology, College of Pharmacy, Al-Nahrain University, Baghdad, Iraq.
Angiogenesis is an intricate pathway that involves the formation of new blood capillaries from old, functioning ones. Improper angiogenesis is a feature of numerous maladies, including malignancy and autoimmune disorders. Indole-related derivatives are believed to interfere with the mitotic spindle, inhibiting the multiplication, and invasion of cancerous human cells.
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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