Knowledge of Aurora A kinase functions is limited to premetaphase events, particularly centrosome maturation, G2/M transition, and mitotic spindle assembly. The involvement of Aurora A in events after metaphase has only been suggested because appropriate experiments are technically difficult. We report here the design of the first human Aurora A kinase (as-AurA) engineered by chemical genetics techniques. This kinase is fully functional biochemically and in cells, and is rapidly and specifically inhibited by the ATP analogue 1-Naphthyl-PP1 (1-Na-PP1). By treating cells exclusively expressing the as-AurA with 1-Na-PP1, we discovered that Aurora A is required for central spindle assembly in anaphase through phosphorylation of Ser 19 of P150Glued. This paper thus describes a new Aurora A function that takes place after the metaphase-to-anaphase transition and a new powerful tool to search for and study new Aurora A functions.
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http://dx.doi.org/10.1083/jcb.201210060 | 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 PDFNat Cell Biol
January 2025
Department of Biochemistry, University of Oxford, Oxford, UK.
Delays in mitosis trigger p53-dependent arrest in G1 of the next cell cycle, thus preventing repeated cycles of chromosome instability and aneuploidy. Here we show that MDM2, the p53 ubiquitin ligase, is a key component of the timer mechanism triggering G1 arrest in response to prolonged mitosis. This timer function arises due to the attenuation of protein synthesis in mitosis.
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.
View Article and Find Full Text PDFProteins
January 2025
Department of Chemistry and Chemical Biology, Indian Institute of Technology (Indian School of Mines), Dhanbad, India.
MPS1 kinase is a dual specificity kinase that plays an important role in the spindle assembly checkpoint mechanism during cell division. Overexpression of MPS1 kinase is reported in several cancers. However, drug discovery and development efforts targeting MPS1 kinase did not result in any clinically successful candidates.
View Article and Find Full Text PDFMol Biol Cell
January 2025
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
SPOP is a Cul3 substrate adaptor responsible for the degradation of many proteins related to cell growth and proliferation. Because mutation or misregulation of SPOP drives cancer progression, understanding the suite of SPOP substrates is important to understanding the regulation of cell proliferation. Here, we identify Nup153, a component of the nuclear basket of the nuclear pore complex, as a novel substrate of SPOP.
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