A novel role of IKKalpha in the mediation of UVB-induced G0/G1 cell cycle arrest response by suppressing Cyclin D1 expression.
Exposure to ultraviolet B (UVB) irradiation (290-320nm 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 IkappaB kinase complex (IKK), IKKalpha, 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 IKKbeta/NF-kappaB activity. We further show that IKKalpha-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 IKKalpha in regulating cell cycle progression during the cellular UVB response. Targeting IKKalpha might be promising for the prevention of UVB-induced cell damage and tumorigenic effects.
Song
Lun
L
Department of Cellular Immunology, Beijing Institute of Basic Medical Sciences, Beijing 100850, People's Republic of China. lunsong@yahoo.com
Dong
Wen
W
Gao
Ming
M
Li
Jingxia
J
Hu
Meiru
M
Guo
Ning
N
Huang
Chuanshu
C
D000818:Animals; D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects*; D019938:Cyclin D1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012867:Skin / Q000528:radiation effects; D013472:Sunlight; D014466:Ultraviolet Rays / Q000009:adverse effects
D016328:NF-kappa B; D019938:Cyclin D1; D051550:I-kappa B Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D046988:Proteasome Endopeptidase Complex