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FUSION PROTEINS COMPRISING A DIMERIZATION, TRIMERIZATION OR TETRAMERIZATION DOMAIN AND AN ADDITIONAL HETEROLOGOUS TRANSCRIPTION ACTIVATION, TRANSCRIPTION REPRESSION, DNA BINDING OR LIGAND BINDING DOMAIN
FUSION PROTEINS COMPRISING A DIMERIZATION, TRIMERIZATION OR TETRAMERIZATION DOMAIN AND AN ADDITIONAL HETEROLOGOUS TRANSCRIPTION ACTIVATION, TRANSCRIPTION REPRESSION, DNA BINDING OR LIGAND BINDING DOMAIN
The present invention relates to novel fusion proteins which activatetranscription, to nucleic acid constructs encoding the proteins and their usein the genetic engineering of cells. Key fusion proteins of the inventioncontain at least two mutually heterologous domains, one of which being abundling domain. Bundling domains include any domain that induces proteinsthat contain it to form multimers ("bundles") through protein-proteininteractions with each other or with other proteins containing the bundlingdomain. Examples of bundling domains that can be used in the practice of thisinvention include domains such as the lac repressor tetramerization domain,the p53 tetramerization domain, a leucine zipper domain, and domains derivedtherefrom which retain observable bundling activity. Cells are engineered bythe introduction of recombinant nucleic acids encoding the fusion proteins,and in some cases with additional nucleic acid constructs, to render themcapable of ligand-dependent regulation of transcription of a target gene.Administration of the ligand to the cells then regulates (positively, or insome cases, negatively) target gene transcription.
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