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    Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extracts

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    Authors
    Hinchcliffe, Edward H.
    Li, Chuan
    Thompson, Elizabeth A.
    Maller, James L.
    Sluder, Greenfield
    UMass Chan Affiliations
    Department of Cell Biology
    Document Type
    Journal Article
    Publication Date
    1999-02-05
    Keywords
    Animals
    Aphidicolin
    Blastomeres
    *CDC2-CDC28 Kinases
    *Cell Cycle Proteins
    Cell Extracts
    Centrosome
    Cyclin E
    Cyclin-Dependent Kinase 2
    Cyclin-Dependent Kinase Inhibitor p27
    Cyclin-Dependent Kinases
    DNA
    Enzyme Inhibitors
    Microscopy, Confocal
    Microscopy, Fluorescence
    Microscopy, Video
    Microtubule-Associated Proteins
    Ovum
    Protein Kinases
    Protein-Serine-Threonine Kinases
    Proteins
    Recombinant Proteins
    *S Phase
    *Tumor Suppressor Proteins
    Xenopus
    Xenopus Proteins
    Cell Biology
    Life Sciences
    Medicine and Health Sciences
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    Link to Full Text
    https://doi.org/10.1126/science.283.5403.851
    Abstract
    The abnormally high number of centrosomes found in many human tumor cells can lead directly to aneuploidy and genomic instability through the formation of multipolar mitotic spindles. To facilitate investigation of the mechanisms that control centrosome reproduction, a frog egg extract arrested in S phase of the cell cycle that supported repeated assembly of daughter centrosomes was developed. Multiple rounds of centrosome reproduction were blocked by selective inactivation of cyclin-dependent kinase 2-cyclin E (Cdk2-E) and were restored by addition of purified Cdk2-E. Confocal immunomicroscopy revealed that cyclin E was localized at the centrosome. These results demonstrate that Cdk2-E activity is required for centrosome duplication during S phase and suggest a mechanism that could coordinate centrosome reproduction with cycles of DNA synthesis and mitosis.
    Source

    Science. 1999 Feb 5;283(5403):851-4.

    DOI
    10.1126/science.283.5403.851
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/38798
    PubMed ID
    9933170
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    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1126/science.283.5403.851
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      Regulation of CDK1 Activity during the G1/S Transition in S. cerevisiae through Specific Cyclin-Substrate Docking: A Dissertation

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      Post-proliferative cyclin E-associated kinase activity in differentiated osteoblasts: inhibition by proliferating osteoblasts and osteosarcoma cells

      Smith, Elisheva; Frenkel, Baruch; MacLachlan, Timothy K.; Giordano, Antonio; Stein, Janet L.; Lian, Jane B.; Stein, Gary S. (1997-08-01)
      Spontaneous differentiation of normal diploid osteoblasts in culture is accompanied by increased cyclin E associated kinase activity on (1) the retinoblastoma susceptibility protein pRB, (2) the p107 RB related protein, and (3) two endogenous cyclin E-associated substrates of 78 and 105 kD. Activity of the differentiation-related cyclin E complexes (diff.ECx) is not recovered in cdc2 or cdk2 immunoprecipitates. Phosphorylation of both the 105 kD endogenous substrate and the p107 exogenous substrate is sensitive to inhibitory activity (diff.ECx-i) present in proliferating osteoblasts. This inhibitory activity is readily recruited by the cyclin E complexes of differentiated osteoblasts but is not found in cyclin E immunoprecipitates of the proliferating cells themselves. Strong inhibitory activity on diff.ECx kinase activity is excerted by proliferating ROS 17/2.8 osteosarcoma cells. However, unlike the normal diploid cells, the diff.ECx-i activity of proliferating ROS 17/2.8 cells is recovered by cyclin E immunoprecipitation. The cyclin-dependent kinase inhibitor p21CIP1/WAF1 inhibits diff.ECx kinase activity. Thus, our results suggest the existence of a unique regulatory system, possibly involving p21CIP1/WAF1, in which inhibitory activity residing in proliferating cells is preferentially targeted towards differentiation-related cyclin E-associated kinase activity.
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      Snf5 tumor suppressor couples chromatin remodeling, checkpoint control, and chromosomal stability

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