A novel role of IKKα in the mediation of UVB-induced G0/G1 cell cycle arrest response by suppressing Cyclin D1 expression

Exposure to ultraviolet B (UVB) irradiation (290–320 nm wavelength) from sunlight induces a variety of medical problems, including sunburn, immunosuppression and skin cancers. However, the molecular mechanisms related to UVB-induced cell damage and/or mutagenic effects have not been fully defined. Here, we demonstrate that one of the catalytic subunits of the IκB kinase complex (IKK), IKKα, plays a critical role in mediation of the UVB-induced G0/G1 cell cycle arrest response by suppressing Cyclin D1 expression. Notably, IKKa-dependent Cyclin D1 regulation is unrelated to IKKβ/NF-κB activity. We further show that IKKα-dependent downregulation of Cyclin D1 expression in the UVB response results from the reduction of ERK1/2-dependent Cyclin D1 transcription coupled with an increase of p38 kinase-dependent Cyclin D1 proteolysis. Thus, our results have identified the novel role of IKKα in regulating cell cycle progression during the cellular UVB response. Targeting IKKα might be promising for the prevention of UVB-induced cell damage and tumorigenic effects.