CK2 Is a C-Terminal IkappaB Kinase Responsible for NF-kappaB Activation during the UV Response.
NF-kappaB is activated in response to proinflammatory stimuli, infections, and physical stress. While activation of NF-kappaB by many stimuli depends on the IkappaB kinase (IKK) complex, which phosphorylates IkappaBs at N-terminal sites, the mechanism of NF-kappaB activation by ultraviolet (UV) radiation remained enigmatic, as it is IKK independent. We now show that UV-induced NF-kappaB activation depends on phosphorylation of IkappaBalpha at a cluster of C-terminal sites that are recognized by CK2 (formerly casein kinase II). Furthermore, CK2 activity toward IkappaB is UV inducible through a mechanism that depends on activation of p38 MAP kinase. Inhibition of this pathway prevents UV-induced IkappaBalpha degradation and increases UV-induced cell death. Thus, the p38-CK2-NF-kappaB axis is an important component of the mammalian UV response.
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Tomohisa
T
Kato
Mireille
M
Delhase
Alexander
A
Hoffmann
Michael
M
Karin
D001665:Binding Sites / Q000502:physiology; D047390:Casein Kinase II; D004789:Enzyme Activation / Q000528:radiation effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects*; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D021122:Protein Subunits; D000072000:NF-KappaB Inhibitor alpha; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases