Stress signals induce transcriptionally inactive E2F-1 independently of p53 and Rb.
One of the common features of cellular response to stress is cell cycle arrest or apoptosis. E2F is one of the key factors which controls cell cycle progression. Overexpression of E2F-1 can also induce apoptosis. In order to understand the role of E2F-1 in cellular response to stress, we studied the E2F-1 response in various cell lines to different types of stress signals including UV irradiation, cisplatin, etoposide and hypoxia. We showed here that the expression level of E2F-1 can be up regulated by the treatment of DNA damage agents as well as hypoxia. The kinetics of E2F-1 increase was dependent on the types of inducer and was similar to that of p53. However, stress signals can induce E2F-1 expression independently of p53 and Rb. Furthermore, the induced E2F-1 was transcriptionally inactive. All these results suggested that E2F-1 may play a very important role in cellular response to stress and this novel role of E2F-1 is independent of its transactivation function.
O'Connor
D J
DJ
Ludwig Institute for Cancer Research, Imperial College of Science, Technology and Medicine at St. Mary's Campus, Norfolk Place, London W2 1PG, UK.
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D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D015687:Cell Hypoxia; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005047:Etoposide / Q000494:pharmacology; D018384:Oxidative Stress; D016160:Retinoblastoma Protein / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D002945:Cisplatin