Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adenovirus E1a protein (E1A) regulates transcription through interaction with transcription factors bound to DNA, like cAMP response element BP1/ATF2, or through dissociating E2F transcription factor complex. However, it was also reported that E1A can bind to DNA (Chatterjee, P. K., Bruner, M., Flint, S. J., and Harter, M. L. (1988) EMBO J. 7, 835-841), and it is not clear whether DNA binding of E1A is involved in a part of the process of transcriptional regulation by E1A. In this paper, the small region of E1A that is responsible for DNA binding was identified and a point mutant lacking DNA binding activity was constructed. Analysis of deletion mutants of E1A proteins expressed in bacteria showed that a basic region between amino acids 201 and 216 of E1A is essential for DNA binding. Point mutation of arginines at amino acid numbers 205 and 206 to aspartic acids completely abolished the DNA binding activity of E1A. Using this mutant, the requirement of the E1A DNA binding for E1A-dependent transcriptional regulation was examined. trans-Activation of the adenovirus E4 promoter and trans-repression of the human c-erbB-2 promoter by this point mutant were examined by cotransfection experiments. Mutations of the E1A DNA-binding domain affected neither the E1A-induced trans-activation nor trans-repression at all. These results give complete proof that the DNA binding activity of E1A is not required for transcriptional regulation by E1A.
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PMID:Transcriptional regulation by a point mutant of adenovirus-2 E1a product lacking DNA binding activity. 135 75

The paucity of tools that control expression of specific genes in vivo represents a major limitation of functional genomics in mammals; most available small-molecule regulators of transcription-e.g. histone deacetylase inhibitors-exert pan-genomic effects. Recent developments in understanding the role of chromatin in regulating the genome, and of protein-DNA interactions have allowed the development of designed transcription factors that regulate specific genes in vivo (Reik et al., Curr Opin Genet Dev 2002;12:233). These proteins contain two modules: (i) a zinc finger protein (ZFP)-based DNA-binding domain (DBD) designed to recognize a specific sequence (for example, a motif in the promoter of a certain gene); (ii) a functional module (for example, a transcriptional activation or repression domain). Recent data describe the use of such designed transcription factors to regulate a variety of clinically relevant gene targets in human cells: these include MDR1, erythropoietin, erbB-2 and erbB-3, VEGF, and PPARgamma. In the case of VEGF (Liu et al., J Biol Chem 2001;276:11323), proportional upregulation by the designed transcription factor of all three distinct splice isoforms generated by this locus was observed, illuminating the utility of endogenous gene control in therapeutic settings (proper isoform ratio is essential for the proangiogenic function of VEGF). In the case of PPARgamma, use of a transcriptional repressor designed to downregulate the expression of two PPARgamma isoforms allowed "mutation-free reverse genetics" analysis that illuminated a unique role for the PPARgamma2 isoform in adipogenesis (Ren et al., Genes Dev 2002;16:27). The ability to selectively activate or repress specific mammalian genes in vivo using designed transcription factors thus has considerable promise in clinical and in basic science settings.
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PMID:Designed transcription factors as tools for therapeutics and functional genomics. 1221 87