| First Author | Dong W | Year | 2012 |
| Journal | Nucleic Acids Res | Volume | 40 |
| Issue | 7 | Pages | 2940-55 |
| PubMed ID | 22169952 | Mgi Jnum | J:197733 |
| Mgi Id | MGI:5494387 | Doi | 10.1093/nar/gkr1216 |
| Citation | Dong W, et al. (2012) IKKalpha contributes to UVB-induced VEGF expression by regulating AP-1 transactivation. Nucleic Acids Res 40(7):2940-55 |
| abstractText | Exposure to ultraviolet B (UVB) irradiation from sunlight induces the upregulation of VEGF, a potent angiogenic factor that is critical for mediating angiogenesis-associated photodamage. However, the molecular mechanisms related to UVB-induced VEGF expression have not been fully defined. Here, we demonstrate that one of the catalytic subunits of the IkappaB kinase complex (IKK), IKKalpha, plays a critical role in mediating UVB-induced VEGF expression in mouse embryonic fibroblasts (MEFs), which requires IKKalpha kinase activity but is independent of IKKbeta, IKKgamma and the transactivation of NF-kappaB. We further show that the transcriptional factor AP-1 functions as the downstream target of IKKalpha that is responsible for VEGF induction under UVB exposure. Both the accumulation of AP-1 component, c-Fos and the transactivation of AP-1 by UVB require the activated IKKalpha located within the nucleus. Moreover, nuclear IKKalpha can associate with c-Fos and recruit to the vegf promoter regions containing AP-1-responsive element and then trigger phosphorylation of the promoter-bound histone H3. Thus, our results have revealed a novel independent role for IKKalpha in controlling VEGF expression during the cellular UVB response by regulating the induction of the AP-1 component and phosphorylating histone H3 to facilitate AP-1 transactivation. Targeting IKKalpha shows promise for the prevention of UVB-induced angiogenesis and the associated photodamage. |
