Abstract: The invention provides methods and compositions relating to a novel tumor necrosis factor receptor associated factor number six (TRAF6) protein, which transcriptionally activates Nuclear Factor .kappa.B. The invention provides isolated TRAF6 hybridization probes and primers capable of hybridizing with the disclosed TRAF6 gene, nucleic acids encoding the subject TRAF6 proteins, methods of making the subject TRAF6 proteins, and methods of using the subject compositions in diagnosis and drug screening.

Abstract: The invention provides methods and compositions for identifying pharmacological agents useful in the diagnosis or treatment of disease associated with the expression of a gene modulated by an interleukin 4 signal transducer and activator of transcription, IL-4 Stat. IL-4 Stat peptides and IL-4 receptor peptides and nucleic acids encoding such peptides find therapeutic uses. The subject compositions include IL-4 Stat and IL-4 receptor proteins, portions thereof, nucleic acids encoding them, and specific antibodies. The disclosed pharmaceutical screening methods are particularly suited to high-throughput screening where one or more steps are performed by a computer controlled electromechanical robot comprising an axial rotatable arm.

Abstract: The invention provides methods and compositions for identifying pharmacological agents useful in the diagnosis or treatment of disease associated with the expression of a gene modulated by a transcription complex containing at least a human nuclear factor of activated T-cells (hNFAT). The materials include a family of hNFAT proteins, active fragments thereof, and nucleic acids encoding them. The methods are particularly suited to high-throughput screening where one or more steps are performed by a computer controlled electromechanical robot comprising an axial rotatable arm.

Abstract: The invention provides screening assays for identifying an inhibitor of a pathogenic helicase activity, e.g. a helicase derived from a pathogenic infectious organism such as a bacterium, protozoan or fungus. Helicase activity is detected by the solid-phase, preferential capture of retained (non-liberated) single-stranded nucleic acid comprising a detectable label.

Abstract: The invention relates to the Ob gene transcriptional promoter. The subject promoters generally comprise a C/EBP binding site and a novel untranslated Ob gene exon. Ob gene promoters are used in diagnosis and pharmaceutical development. In particular, transfected adipocytes comprising Ob gene promoters operably linked to a reporter are used in high-throughput pharmaceutical screens.

Abstract: The invention provides methods and compositions for identifying pharmacological agents useful in the diagnosis or treatment of disease associated with the expression of a gene modulated by a transcription complex containing at least CBF1 and a transcription factor. The methods involve combining CBF1, the Epstein-Barr virus transcription factor EBNA2 or cellular homolog thereof, and a candidate pharmacological agent. This mixture is incubated under conditions whereby, but for the presence of the candidate pharmacological agent, CBF1 binds EBNA2. The absence of selective binding indicates that the candidate pharmacological agent is capable of selectively modulating the expression of a gene dependent on CBF1-transcription factor binding. The mixture may further comprise a CBF1 binding element including the nucleotide sequence: C-G-T-G-G-G-A-A.

Abstract: The invention relates to human Interleukin-1 Receptor-Associated Protein Kinases (IRAKs), nucleic acids which encode IRAKs and hybridization probes and primers capable of hybridizing with IRAK genes and methods of using the subject compositions; in particular, methods such as IRAK-based in vitro binding assays and phosphorylation assays for screening chemical libraries for lead compounds for pharmacological agents.

Abstract: The invention provides methods and compositions relating to interleukin 12 signal transducers, particularly an isolated human signal transducer and activator of transcription 4 (hStat 4), or a fragment thereof having an hStat 4-specific binding affinity, nucleic acids encoding hStat 4, which nucleic acids may be part of hStat 4-expression vectors and may be incorporated into a recombinant cell, agents which selectively bind hStat 4 or hStat 4 intracellular binding targets, or disrupt the binding of hStat 4 to such intracellular targets, methods of making such agents and hStat 4-specific binding targets in the form of cell surface proteins and nucleic acids. An hStat 4 drug screening assay involves forming mixtures of an hStat 4, an intracellular hStat 4 binding target, and a prospective agent at different concentrations. The mixtures are incubated to permit the binding of the intracellular hStat 4 binding target to the hStat 4 and the mixtures are then analyzed for the presence of such binding.

Abstract: The invention provides promoter specific and promoter non-specific screening assays for identifying an inhibitor of a pathogenic nucleic acid polymerase activity, e.g. an RNA polymerase derived from a pathogenic infectious organism such as a bacterium, protozoan or fungus. Generally, the methods involve forming a mixture of nucleotides, a polynucleotide template, a pathogenic polymerase candidate inhibitor of polymerase activity, where at least one of the nucleotides comprises a detectable label. The mixture is incubated under conditions whereby, but for the presence of the candidate inhibitor, the polymerase transcribes the polynucleotide template by catalyzing the polymerization of the nucleoside triphosphates into a polynucleotide having a nucleotide sequence complementary to that of the polynucleotide template. The nascent transcript is captured by a polynucleotide-selective agent immobilized on a solid substrate for subsequent washing and label detection.

Abstract: The invention provides methods and compositions relating to interleukin 2 signal transducers, particularly an isolated human signal transducer and activator of transcription 5 (hStat 5), or a fragment thereof having an hStat 5-specific binding affinity, nucleic acids encoding hStat 5, which nucleic acids may be part of hStat 5-expression vectors and may be incorporated into a recombinant cell, agents which selectively bind hStat 5 or hStat 5 intracellular binding targets, or disrupt the binding of hStat 5 to such intracellular targets, methods of making such agents and hStat 5-specific binding targets in the form of cell surface proteins and nucleic acids. An hStat 5 drug screening assay involves forming mixtures of an hStat 5, an intracellular hStat 5 binding target, and a prospective agent at different concentrations. The mixtures are incubated to permit the binding of the intracellular hStat 5 binding target to the hStat 5 and the mixtures are then analyzed for the presence of such binding.

Abstract: The invention provides methods and compositions for identifying pharmacological agents useful in the diagnosis or treatment of disease associated with the expression of a gene modulated by a transcription complex containing at least a human nuclear factor of activated T-cells (hNFAT). The materials include a family of hNFAT proteins, active fragments thereof, and nucleic acids encoding them. The methods are particularly suited to high-throughput screening where one or more steps are performed by a computer controlled electromechanical robot comprising an axial rotatable arm.

Abstract: The invention provides methods and compositions for identifying pharmacological agents useful in the diagnosis or treatment of disease associated with the expression of a gene modulated by an interleukin 4 signal transducer and activator of transcription, IL-4 Stat. IL-4 Stat peptides and IL-4 receptor peptides and nucleic acids encoding such peptides find therapeutic uses. The subject compositions include IL-4 Stat and IL-4 receptor proteins, portions thereof, nucleic acids encoding them, and specific antibodies. The disclosed pharmaceutical screening methods are particularly suited to high-throughput screening where one or more steps are performed by a computer controlled electromechanical robot comprising an axial rotatable arm.

Abstract: Host Cell Factor (HCF), a eukaryotic cellular protein involved in transcription, nucleic acids encoding HCF, and methods of using HCF and HCF-encoding nucleic acids are provided. HCF activity is disclosed to comprise a collection of polypeptides encoded by a structural gene encoding a parent protein of 2039 amino acids. HCF-specific binding compounds are disclosed including antibodies to HCF epitopes. Because HCF is required for the transcription of a number of viral genes such as the immediate early genes of Herpes Simplex Virus, the invention provides HCF-based pharmaceutical compositions and HCF-based methods for screening chemical libraries for regulators of viral transcription. Such compositions are used in the treatment of viral infections by modulating the transcription of certain viral genes.

Abstract: Pharmacological agents useful in the diagnosis or treatment of disease associated with the expression of a gene are identified in high throughput drug screening assays. The methods involve combining a labeled transcription factor, a nucleic acid coupled to a ligand, a candidate pharmacological agent and a receptor immobilized on a solid substrate, such as a microtiter plate, filter, or bead. The nucleic acid has at least that portion of a nucleotide sequence naturally involved in the regulation of the transcription of the gene which is necessary for sequence-specific interaction with the transcription factor. The resultant combination is incubated under conditions whereby the receptor is bound to the ligand and, but for the presence of said candidate pharmacological agent, the transcription factor is sequence-specifically bound to the nucleic acid. Unbound transcription factor is then removed or washed from the solid substrate and labelled, sequence-specifically bound transcription factor is detected.

Abstract: A novel family of intracellular signaling proteins, exemplified by a Tumor Necrosis Factor Receptor-1 Associated Death Domain protein (TRADD), share a common TRADD sequence and include transducers of signals that modulate cell growth, differentiation and apoptosis. As such, the TRADD proteins, TRADD-encoding nucleic acids, and natural TRADD intracellular binding targets provide both important targets and means for therapeutic intervention. In particular, the invention provides isolated TRADDs and TRADD fragments, nucleic acids encoding the subject TRADDs and TRADD fragments or capable of selectively hybridizing to such TRADD-encoding nucleic acids, vectors and cells comprising TRADD-encoding nucleic acids, and TRADD-specific binding reagents. These compositions find use in diagnostic and therapeutic methods for disease associated with undesirable cell growth, migration, differentiation and/or cytokine signal responsiveness and methods and compositions for identifying lead compounds and pharmacological agents.

Abstract: Host Cell Factor (HCF), a eukaryotic cellular protein involved in transcription, nucleic acids encoding HCF, and methods of using HCF and HCF-encoding nucleic acids are provided. HCF activity is disclosed to comprise a collection of polypeptides encoded by a structural gene encoding a parent protein of 2039 amino acids. HCF-specific binding compounds are disclose including antibodies to HCF epitopes. Because HCF is required for the transcription of a number of vital genes such as the immediate early genes of Herpes Simplex Virus, the invention provides HCF-based methods for screening chemical libraries for regulators of viral transcription. Such regulators are used in the treatment of viral infections by modulating the transcription of certain viral genes.