Regulation of epidermal apoptosis and DNA repair by E2F1 in response to ultraviolet B radiation.
The E2F1 transcription factor regulates the expression of genes involved in cell proliferation, apoptosis and DNA repair. Following DNA damage, E2F1 is phosphorylated and stabilized, but the physiological role of E2F1 in the response to DNA damage is unclear. We find that mice lacking E2F1 have increased levels of epidermal apoptosis compared to wild-type mice following exposure to ultraviolet B (UVB) radiation. Moreover, transgenic overexpression of E2F1 in basal layer keratinocytes suppresses apoptosis induced by UVB. Inhibition of UVB-induced apoptosis by E2F1 is unexpected given that most studies have demonstrated a proapoptotic function for E2F1. E2F1-mediated suppression of apoptosis does not involve alterations in mitogen-activated protein kinase activation or Bcl-2 downregulation in response to UVB and is independent of p53. Instead, inhibition of UVB-induced apoptosis by E2F1 correlates with a stimulation of DNA repair. Mice lacking E2F1 are impaired for the removal of DNA photoproducts, while E2F1 transgenic mice repair UVB-induced DNA damage at an accelerated rate compared to wild-type mice. These findings suggest that E2F1 participates in the response to UVB by promoting DNA repair and suppressing apoptosis.
Berton
Thomas R
TR
Department of Carcinogenesis, Science Park Research Division, The University of Texas MD Anderson Cancer Center, PO Box 389, 1808 Park Road 1C, Smithville, TX 78957, USA.
Mitchell
David L
DL
Guo
Ruifeng
R
Johnson
David G
DG
D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000494:pharmacology*; D049109:Cell Proliferation; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004817:Epidermis / Q000502:physiology*; D005260:Female; D016158:Genes, p53; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012878:Skin Neoplasms / Q000235:genetics / Q000503:physiopathology; D014157:Transcription Factors / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D014157:Transcription Factors