Kato Tomohisa, Delhase Mireille, Hoffmann Alexander, Karin Michael
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.
Mol Cell. 2003 Oct;12(4):829-39. doi: 10.1016/s1097-2765(03)00358-7.
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.
核因子κB（NF-κB）在对促炎刺激、感染和物理应激的反应中被激活。虽然许多刺激激活NF-κB依赖于IκB激酶（IKK）复合物，该复合物在N端位点使IκB磷酸化，但紫外线（UV）辐射激活NF-κB的机制仍不清楚，因为它不依赖IKK。我们现在表明，紫外线诱导的NF-κB激活依赖于IκBα在C端位点簇的磷酸化，这些位点可被CK2（以前称为酪蛋白激酶II）识别。此外，CK2对IκB的活性可通过依赖p38丝裂原活化蛋白激酶（MAP激酶）激活的机制被紫外线诱导。抑制该途径可防止紫外线诱导的IκBα降解并增加紫外线诱导的细胞死亡。因此，p38-CK2-NF-κB轴是哺乳动物紫外线反应的重要组成部分。
