Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Within the region around 150 bp upstream of the initiation codon, which was previously shown to suffice for growth-regulated expression, the murine thymidine kinase gene carries a single binding site for transcription factor Sp1; about 10 bp downstream of this site, there is a binding motif for transcription factor E2F. The latter protein appears to be responsible for growth regulation of the promoter. Mutational inactivation of either the Sp1 or the E2F site almost completely abolishes promoter activity, suggesting that the two transcription factors interact directly in delivering an activation signal to the basic transcription machinery. This was verified by demonstrating with the use of glutathione S-transferase fusion proteins that E2F and Sp1 bind to each other in vitro. For this interaction, the C-terminal part of Sp1 and the N terminus of E2F1, a domain also present in E2F2 and E2F3 but absent in E2F4 and E2F5, were essential. Accordingly, E2F1 to E2F3 but not E2F4 and E2F5 were found to bind sp1 in vitro. Coimmunoprecipitation experiments showed that complexes exist in vivo, and it was estabilished that the distance between the binding sites for the two transcription factors was critical for optimal promoter activity. Finally, in vivo footprinting experiments indicated that both the sp1 and E2F binding sites are occupied throughout the cell cycle. Mutation of either binding motif abolished binding of both transcription factors in vivo, which may indicate cooperative binding of the two proteins to chromatin-organized DNA. Our data are in line with the hypothesis that E2F functions as a growth- and cell cycle regulated tethering factor between Sp1 and the basic transcription machinery.
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PMID:Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F. 865 41

Various studies point to the potential role of combinatorial action of transcription factors as a mechanism to achieve the complexity of eukaryotic gene control with a finite number of regulatory proteins. Our previous work has focused on interactions involving the E2F family of transcription factors as an example of combinatorial gene control, leading to the identification of TFE3 and YY1 as transcription partners for several E2F proteins. We now show that additional E2F target genes share a common promoter architecture and are also regulated by the combined action of TFE3 and E2F3. In contrast, the thymidine kinase (TK-1) promoter is also regulated by E2F3 but independent of TFE3. Other promoters exhibit distinct specificity in the interaction with E2F proteins that includes a role for E2F1 but not E2F3, examples where both E2F1 and E2F3 are seen to interact, and promoters that are regulated by TFE3 but independent of an E2F. We propose that these examples of combinatorial interactions involving E2F proteins provide a basis for the specificity of transcription control in the Rb/E2F pathway.
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PMID:Combinatorial gene control involving E2F and E Box family members. 1501 47