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Publication : Regulation of Egr-1-dependent gene expression by the C-terminal activation domain.

First Author  Gosslar U Year  1999
Journal  Biochem Biophys Res Commun Volume  255
Issue  2 Pages  208-15
PubMed ID  10049687 Mgi Jnum  J:53073
Mgi Id  MGI:1331258 Doi  10.1006/bbrc.1999.0182
Citation  Gosslar U, et al. (1999) Regulation of Egr-1-dependent gene expression by the C-terminal activation domain. Biochem Biophys Res Commun 255(2):208-15
abstractText  The present study analyzes the role of the C-terminal activation domain for Egr-1 transcriptional activity using N-terminal deletion mutants. Mutant N372 comprising the entire C-terminal activation domain and partly truncated DNA-binding and nuclear translocation domains functioned as the transdominant repressor of Egr-1-dependent gene transcription. Activity of the SV40 promoter, however, was not affected by the N372 mutant. Analysis of additional Egr-1 mutants revealed that the transdominant negative effect of N372 was dependent on truncation of the zinc finger motifs that mediate DNA binding. Reconstitution of the zinc fingers was sufficient to generate Egr-1 proteins with potent transcriptional activity. The inhibitory mutant N372 is efficiently translocated to the nucleus, but fails to bind DNA and does not displace DNA-bound wildtype Egr-1. These results provide evidence for an Egr-1-specific cofactor that interacts with the C-terminal activation domain and is essential for Egr-1 transcriptional activity. Copyright 1999 Academic Press.
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