Luan Bing, Zhang Zhenning, Wu Yalan, Kang Jiuhong, Pei Gang
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
EMBO J. 2005 Dec 21;24(24):4237-46. doi: 10.1038/sj.emboj.7600882. Epub 2005 Nov 24.
NF-kappaB activation is an important mechanism of mammalian UV response to protect cells. UV-induced NF-kappaB activation depends on the casein kinase II (CK2) phosphorylation of IkappaBalpha at a cluster of C-terminal sites, but how it is regulated remains unclear. Here we demonstrate that beta-arrestin2 can function as an effective suppressor of UV-induced NF-kappaB activation through its direct interaction with IkappaBalpha. CK2 phosphorylation of beta-arrestin2 blocks its interaction with IkappaBalpha and abolishes its suppression of NF-kappaB activation, indicating that the beta-arrestin2 phosphorylation is critical. Moreover, stimulation of beta2-adrenergic receptors, a representative of G-protein-coupled receptors in epidermal cells, promotes dephosphorylation of beta-arrestin2 and its suppression of NF-kappaB activation. Consequently, the beta-arrestin2 suppression leads to promotion of UV-induced cell death, which is also under regulation of beta-arrestin2 phosphorylation. Thus, beta-arrestin2 is identified as a phosphorylation-regulated suppressor of UV response and this may play a functional role in the response of epidermal cells to UV.
核因子-κB（NF-κB）激活是哺乳动物紫外线（UV）应答以保护细胞的重要机制。紫外线诱导的NF-κB激活依赖于酪蛋白激酶II（CK2）对IκBα C末端位点簇的磷酸化作用，但对其调控方式仍不清楚。在此，我们证明β-抑制蛋白2可通过与IκBα直接相互作用，作为紫外线诱导的NF-κB激活的有效抑制剂。β-抑制蛋白2的CK2磷酸化会阻断其与IκBα的相互作用，并消除其对NF-κB激活的抑制作用，这表明β-抑制蛋白2的磷酸化至关重要。此外，刺激β2-肾上腺素能受体（表皮细胞中G蛋白偶联受体的代表）可促进β-抑制蛋白2的去磷酸化及其对NF-κB激活的抑制作用。因此，β-抑制蛋白2的抑制作用会导致紫外线诱导的细胞死亡增加，而这也受β-抑制蛋白2磷酸化的调控。因此，β-抑制蛋白2被确定为紫外线应答的磷酸化调节抑制剂，这可能在表皮细胞对紫外线的应答中发挥功能作用。
