The Salk Institute for Biological Studies

Anthony E Oro

Ronald Mark Evans

Tso-Pang Yao

David John Mangelsdorf

Estelita S Ong

Vincent Giguere

Uwe K Borgmeyer

William A Segraves

Stanley M Hollenberg

Michael B Mc Keown

Richard Alan Heyman

Michael B McKeown

Klaus Damm

In accordance with the present invention, it has been discovered that various members of the steroid/thyroid superfamily of receptors can interact with the insect-derived ultraspiracle receptor, to form multimeric species. Accordingly, the interaction of at least one member of the steroid/thyroid superfamily of receptors with at least the dimerization domain of the ultraspiracle receptor modulates the ability of said member of the steroid/thyroid superfamily of receptors to transactivate transcription of genes maintained under hormone expression control in the presence of the cognate ligand for said member of the superfamily.

Multimeric forms of members of the steroid/thyroid superfamily of receptors with the ultraspiracle receptor

In accordance with the present invention, it has been discovered that various members of the steroid/thyroid superfamily of receptors can interact with the insect-derived ultraspiracle receptor, to form multimeric species. Accordingly, the interaction of at least one member of the steroid/thyroid superfamily of receptors with at least the dimerization domain of the ultraspiracle receptor modulates the ability of said member of the steroid/thyroid superfamily of receptors to trans-activate transcription of genes maintained under hormone expression control in the presence of the cognate ligand for said member of the superfamily.

Methods of modulating the expression of genes using ultraspiracle receptor

Novel members of the steroid/thyroid superfamily of receptors are described. DNA sequences encoding same, expression vectors containing such DNA and host cells transformed with such expression vectors are also disclosed, as are methods for the expression of the novel receptors of the invention, and various uses thereof.

Methods of using novel steroid hormone orphan receptors

Orphan steroid hormone receptors

The present invention relates to the discovery of novel insect receptor polypeptides, which, when complexed with certain ligands, or otherwise activated by certain compounds, modulate transcription of certain genes by binding to cognate response elements associated with the promoters of the genes. The novel receptors of the invention are substantially similar to previously discovered mammalian receptors which are activated to modulate transcription of certain genes in cells, when the cells are exposed to retinoic acid. The invention provides DNAs encoding the novel receptors, including expression vectors for expression of the receptors in cells; cells transformed with such expression vectors; cells co-transformed with such expression vectors and with reporter vectors to monitor activation of the receptors to modulate transcription, when the cells are exposed to ligand for the invention receptor; and methods of using such co-transformed cells in screening for compounds which are capable of leading to activation of the receptors and for compounds which are capable of interfering with such activation and, as such, are potentially potent insecticides. The invention also provides DNA and RNA probes for identifying DNA's encoding related receptors, of insects and other animals, of the class, to which the novel receptors of the invention belong.

Insect retinoid-like receptor compositions and methods

Dominant negative chimeras of the steroid/thyroid superfamily of

Disclosed is an analysis of domains of receptors of the steroid/thyroid hormone superfamily, and particularly of the glucocorticoid receptor, to identify requirements for the trans-acting transcriptional repression activities of the receptors. Based on the analysis, certain novel receptor analogs are provided, as are various novel DNAs, expression vectors, cells and transgenic animals as well as novel methods of using trans-acting transcription-repressing analogs of the receptors in various applications. These applications include gene therapy, screening of cells in culture or transgenic animals for compositions effective to treat various diseases due to inability to properly respond to hormones of the steroid or thyroid hormone group, and screening of cells in culture for ligands that are capable, upon binding to one of the receptors, to activate its trans-acting transcription activating and trans-acting transcription-repressing activities.

Receptor transcription-repression activity compositions and methods

Receptors

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Anthony E Oro