The p38 and ERK MAP kinase pathways cooperate to activate Ternary Complex Factors and c-fos transcription in response to UV light.
We investigated the activation of c-fos transcription following UV irradiation, a 'stress' stimulus. In both HeLa TK- and NIH 3T3 cells the Serum Response Element is required for efficient UV-induced c-fos transcription, and in HeLa TK- cells the Ternary Complex Factor (TCF) binding site contributes substantially to activation. Consistent with this, UV irradiation activates LexA-TCF fusion proteins more strongly in HeLa TK- than in NIH 3T3 cells. The TCF C-termini of the TCFs are substrates for UV-induced MAP kinases: both the Elk-1 and SAP-1a C-termini are efficiently phosphorylated by the p38 MAPK, but only the Elk-1 C-terminus is a good substrate for the SAPK/JNKs. The specificity and activation kinetics of TCF C-terminal kinases, and the susceptibility of transcriptional activation by LexA-TCF fusion proteins to specific inhibitors of different MAPK pathways, show that both the ERK and p38 MAPK pathways contribute to TCF activation in response to UV irradiation. Activity of both these pathways is also required for the response of the c-fos gene itself to UV stimulation.
Price
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MA
Transcription Laboratory, Imperial Cancer Research Fund Laboratories, London, UK.
Cruzalegui
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Treisman
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D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000528:radiation effects; D016762:Genes, fos / Q000528:radiation effects*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000528:radiation effects; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism / Q000528:radiation effects; D014158:Transcription, Genetic / Q000528:radiation effects*; D014466:Ultraviolet Rays; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4
D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; C494193:ELK4 protein, human; C494113:Elk1 protein, mouse; C494194:Elk4 protein, mouse; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4; D017871:Calcium-Calmodulin-Dependent Protein Kinases