Delphine Gerber-Scokaert
Implication of protein kinase CK2 in the response to cellular stress. Study of the regulatory mechanisms involved in the regulation of CK2
Published on 20 October 2000
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Thesis presented October 20, 2000
Abstract:
The protein kinase CK2 is a highly conserved serine/threonine protein kinase composed of two distinct subunits, a catalytic α subunit and a regulatory ß subunit. Although it has been involved in many cellular processes including proliferation and differentiation, its exact function remains elusive. During this thesis, the role of CK2 during cellular stress has been addressed. This work indeed shows that in response to particular cellular stresses (heat shock and UV irradiation) the protein kinase CK2 relocalizes in specific regions inside the nucleus that appear as speckle-like granules in the interchromatine space. Electron microscopic analysis shows a fibrillar composition for these granules and reveals that the two CK2 subunits are differentially targeted inside the nucleus after heat stress since only the catalytic α subunit colonizes the nucleolus in this condition. Such a relocalization of the kinase in response to hyperthermia takes place in a time and dose dependent manner and is reversible at 37°C. These observations suggest strongly that CK2 is involved in the response to cellular stresses although it does not provide any evidence for a positive or a detrimental role of the kinase in the survival of the cell in challenging conditions. During this thesis, the mechanism by which CK2 is targeted to the nucleus after heat shock has also been studied. The results show that although several phosphorylation sites are present on both CK2 subunits and these sites have been shown to be modified after serum stimulation, phosphorylation may not be involved in the heat-induced relocalization of CK2. However, our date suggest that CK2 is retained in the cytoplasmic fraction in control conditions by an anchoring mechanism that is disrupted upon heat shock.
Keywords:
CK2, Protein kinase, cellular stress, heat shock, relocalization
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