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  • The Company of Biologists  (2)
  • 1
    Online Resource
    Online Resource
    The Company of Biologists ; 2022
    In:  Journal of Cell Science Vol. 135, No. 6 ( 2022-03-15)
    In: Journal of Cell Science, The Company of Biologists, Vol. 135, No. 6 ( 2022-03-15)
    Abstract: Mammalian oocytes are arrested at meiotic prophase I. The dual-specificity phosphatase CDC25B is essential for cyclin-dependent kinase 1 (CDK1) activation that drives resumption of meiosis. CDC25B reverses the inhibitory effect of the protein kinases WEE1 and MYT1 on CDK1 activation. Cdc25b−/− female mice are infertile because oocytes cannot activate CDK1. To identify a role for CDC25B following resumption of meiosis, we restored CDK1 activation in Cdc25b−/− oocytes by inhibiting WEE1 and MYT1, or expressing EGFP-CDC25A or constitutively active EGFP-CDK1 from microinjected complementary RNAs. Forced CDK1 activation in Cdc25b−/− oocytes allowed resumption of meiosis, but oocytes mostly arrested at metaphase I (MI) with intact spindles. Similarly, approximately a third of Cdc25b+/− oocytes with a reduced amount of CDC25B arrested in MI. MI-arrested Cdc25b−/− oocytes also displayed a transient decrease in CDK1 activity similar to Cdc25b+/+ oocytes during the MI-MII transition, whereas Cdc25b+/− oocytes exhibited only a partial anaphase-promoting complex/cyclosome activation and anaphase I entry. Thus, CDC25B is necessary for the resumption of meiosis and the MI-MII transition.
    Type of Medium: Online Resource
    ISSN: 0021-9533 , 1477-9137
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2022
    detail.hit.zdb_id: 219171-4
    detail.hit.zdb_id: 1483099-1
    SSG: 12
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    The Company of Biologists ; 2013
    In:  Journal of Cell Science
    In: Journal of Cell Science, The Company of Biologists
    Abstract: Polo-like kinase-1 (Plk1) is required for proper cell division. Activation of Plk1 requires phosphorylation on a conserved threonine in the T-loop of the kinase domain (T210). Plk1 is first phosphorylated on T210 in G2 phase by the kinase Aurora-A, in concert with its cofactor Bora. However, Bora was shown to be degraded prior to entry into mitosis, and it is currently unclear how Plk1 activity is sustained in mitosis. Here we show that the Bora/Aurora-A complex remains the major activator of Plk1 in mitosis. We show that a small amount of Aurora-A activity is sufficient to phosphorylate and activate Plk1 in mitosis. In addition, a fraction of Bora is retained in mitosis, which is essential for continued Aurora-A dependent T210 phosphorylation of Plk1. We find that once Plk1 is activated, minimal amounts of the Bora/Aurora-A complex are sufficient to sustain Plk1 activity. Thus, the activation of Plk1 by Aurora-A may function as a bistable switch; highly sensitive to inhibition of Aurora-A in its initial activation, but refractory to fluctuations in Aurora-A activity once Plk1 is fully activated. This provides a cell with robust Plk1 activity once it has committed to mitosis.
    Type of Medium: Online Resource
    ISSN: 1477-9137 , 0021-9533
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2013
    detail.hit.zdb_id: 219171-4
    detail.hit.zdb_id: 1483099-1
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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