Induction and activation of the p53 pathway: a role for the protein kinase CK2?

David W Meek, Miranda Cox

    Research output: Contribution to journalArticlepeer-review

    18 Citations (Scopus)

    Abstract

    Protein kinase CK2 has many established in vitro substrates, but it is only within the past few years that we have begun to ascertain which of these are its real physiological targets, how their phosphorylation may contribute towards regulating normal cell physiology, and how phosphorylation of these proteins might influence the development of diseases such as cancer. One of the well-characterised in vitro substrates for CK2 is the tumour suppressor protein, p53. However, the physiological nature of this interaction has never been fully established. In the present article, we summarise a recent study from our laboratory showing that phosphorylation of p53 at Ser392, the sole site modified by CK2 in vitro, is regulated by a novel mechanism where the stoichiometry of phosphorylation is governed by the rate of turnover of the p53 protein. Such a model is entirely consistent with phosphorylation by a constitutively active protein kinase such as CK2. In contrast to this, while there is overwhelming evidence that CK2 phosphorylates p53 in vitro and is the only detectable Ser392 protein kinase in cell extracts, our data raise uncertainty as to whether this interaction truly reflects events underpinning Ser392 phosphorylation in vivo. We consider the possible role of CK2 in regulating the p53 response in a wider context and suggest key issues that should be addressed experimentally to provide a more cohesive picture of the relationship between this important protein kinase and a pivotal anti-cancer surveillance system in cells.

    Original languageEnglish
    Pages (from-to)133-138
    Number of pages6
    JournalMolecular and Cellular Biochemistry
    Volume356
    Issue number1-2
    DOIs
    Publication statusPublished - 2011

    Keywords

    • Protein kinase CK2
    • p53
    • Phosphorylation
    • Serine 392
    • TUMOR-SUPPRESSOR PROTEIN
    • CDK9 PHOSPHORYLATES P53
    • DNA-DAMAGE
    • SER389 PHOSPHORYLATION
    • IONIZING-RADIATION
    • GAMMA-RADIATION
    • SERINE 389
    • MDM2
    • SITE
    • UV

    Fingerprint

    Dive into the research topics of 'Induction and activation of the p53 pathway: a role for the protein kinase CK2?'. Together they form a unique fingerprint.

    Cite this