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The effects of copper modulation on CK2 kinase activity
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The effects of copper modulation on CK2 kinase activity

Fatimah Alfaran
Master of Science (M.S.), Drexel University
Jul 2020
DOI:
https://doi.org/10.17918/00000262
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Abstract

Protein kinases facilitate the phosphorylation of target substrates involved in a number of critical signaling pathways. Casein kinase 2 (CK2) is a highly conserved acidophilic serine/threonine kinase that is ubiquitously expressed and has hundreds of confirmed and predicted substrates. A significant percentage of these substrates plays important roles in cell growth and proliferation, implicating this kinase in the progression of cancer. Indeed, overexpression of CK2 has been detected across multiple cancer types and is generally associated with poor patient outcomes. With regard to enzymatic activity, CK2 is an unusual kinase that exhibits apparent constitutive activity. While CK2 is active in the absence of most extracellular stimuli and intracellular signals, it is hypothesized that a mechanism of regulation likely exists and has yet to be identified. In the present study, we show that CK2 binds directly to the transition metal copper and that this binding enhances CK2 kinase activity in vitro. We additionally demonstrate that this enhanced activity is specific for copper and does not occur in the presence of other metals. Moreover, via overexpression of the primary mammalian copper importer Ctr1, we show that CK2 activity is enhanced when intracellular copper levels are elevated. Together our data suggest that CK2 activity is regulated by copper availability, findings that may have clinical relevance in treating cancers driven by aberrant CK2 signaling.

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