CK2 Is a C-Terminal IkappaB Kinase Responsible for NF-kappaB Activation during the UV Response

Mol Cell. 2003 Oct;12(4):829-39. doi: 10.1016/s1097-2765(03)00358-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites / physiology
  • Casein Kinase II
  • Enzyme Activation / radiation effects
  • Humans
  • I-kappa B Proteins / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Phosphorylation / radiation effects
  • Protein Structure, Tertiary / physiology
  • Protein Subunits / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • Signal Transduction / physiology
  • Signal Transduction / radiation effects*
  • Ultraviolet Rays*
  • p38 Mitogen-Activated Protein Kinases

Substances

  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Protein Subunits
  • NF-KappaB Inhibitor alpha
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases