Beta-arrestin2 functions as a phosphorylation-regulated suppressor of UV-induced NF-kappaB activation.
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.
Luan
Bing
B
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.
Zhang
Zhenning
Z
Wu
Yalan
Y
Kang
Jiuhong
J
Pei
Gang
G
D017209:Apoptosis; D019390:Arrestins / Q000378:metabolism / Q000502:physiology*; D001665:Binding Sites; D047390:Casein Kinase II / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002469:Cell Separation; D053938:DNA Fragmentation; D004307:Dose-Response Relationship, Radiation; D004817:Epidermis / Q000528:radiation effects; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D020287:In Situ Nick-End Labeling; D008954:Models, Biological; D015233:Models, Statistical; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D014466:Ultraviolet Rays; D000071557:beta-Arrestins
D019390:Arrestins; D016328:NF-kappa B; D043562:Receptors, G-Protein-Coupled; D013778:Tetrazolium Salts; D013844:Thiazoles; D000071557:beta-Arrestins; D047390:Casein Kinase II; C022616:thiazolyl blue