FUSION PROTEINS COMPRISING A DIMERIZATION, TRIMERIZATION OR TETRAMERIZATION DOMAIN AND AN ADDITIONAL HETEROLOGOUS TRANSCRIPTION ACTIVATION, TRANSCRIPTION REPRESSION, DNA BINDING OR LIGAND BINDING DOMAIN

摘要

The present invention relates to novel fusion proteins which activate transcription, to nucleic acid constructs encoding the proteins and their use in the genetic engineering of cells. Key fusion proteins of the invention contain at least two mutually heterologous domains, one of which being a bundling domain. Bundling domains include any domain that induces proteins that contain it to form multimers ('bundles') through protein-protein interactions with each other or with other proteins containing the bundling domain. Examples of bundling domains that can be used in the practice of this invention include domains such as the lac repressor tetramerization domain, the p53 tetramerization domain, a leucine zipper domain, and domains derived therefrom which retain observable bundling activity. Cells are engineered by the introduction of recombinant nucleic acids encoding the fusion proteins, and in some cases with additional nucleic acid constructs, to render them capable of ligand-dependent regulation of transcription of a target gene. Administration of the ligand to the cells then regulates (positively, or in some cases, negatively) target gene transcription.