The regulatory beta-subunit of protein kinase CK2 regulates cell-cycle progression at the onset of mitosis

C. W. Yde, B. B. Olsen, D. Meek, N. Watanabe, B. Guerra

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    43 Citations (Scopus)

    Abstract

    Cell-cycle transition from the G(2) phase into mitosis is regulated by the cyclin-dependent protein kinase 1 (CDK1) in complex with cyclin B. CDK1 activity is controlled by both inhibitory phosphorylation, catalysed by the Myt1 and Wee1 kinases, and activating dephosphorylation, mediated by the CDC25 dual-specificity phosphatase family members. In somatic cells, Wee1 is downregulated by phosphorylation and ubiquitin-mediated degradation to ensure rapid activation of CDK1 at the beginning of M phase. Here, we show that downregulation of the regulatory beta-subunit of protein kinase CK2 by RNA interference results in delayed cell-cycle progression at the onset of mitosis. Knockdown of CK2 beta causes stabilization of Wee1 and increased phosphorylation of CDK1 at the inhibitory Tyr15. PLK1-Wee1 association is an essential event in the degradation of Wee1 in unperturbed cell cycle. We have found that CK2 beta participates in PLK1-Wee1 complex formation whereas its cellular depletion leads to disruption of PLK1-Wee1 interaction and reduced Wee1 phosphorylation at Ser53 and 121. The data reported here reinforce the notion that CK2 beta has functions that are independent of its role as the CK2 regulatory subunit, identifying it as a new component of signaling pathways that regulate cell-cycle progression at the entry of mitosis.

    Original languageEnglish
    Pages (from-to)4986-4997
    Number of pages12
    JournalOncogene
    Volume27
    Issue number37
    DOIs
    Publication statusPublished - 28 Aug 2008

    Keywords

    • CK2 beta
    • Wee1
    • PLK1
    • CDC25A
    • cell cycle
    • DNA-DAMAGE
    • IONIZING-RADIATION
    • NEGATIVE REGULATION
    • CDC25A PHOSPHATASE
    • SOMATIC WEE1
    • INDUCED S
    • CHECKPOINT
    • PHOSPHORYLATION
    • DEGRADATION
    • CHK1

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