Abstract: Each gene in a group comprising many genes is cloned into an expression vector so that its gene product should be expressed as a fusion protein with a protein emitting self-fluorescence to construct a gene expression library. The gene expression library is introduced into cells of two groups to express the fusion proteins in the cells, and only one cell group is stimulated by a drug or the like. Then, cells in which the fusion proteins are localized in the nuclei or their nuclei are isolated from cells of the two groups, respectively. By comparing these cells, genes coding for proteins that are transported into the nuclei specifically in response to a certain stimulus when the stimulus is applied to the cells are retrieved.

Abstract: The invention provides mammalian cDNAs which encode mammalian vesicle membrane proteins. It also provides for the use of the cDNAs, fragments, complements, and variants thereof and of the encoded proteins, portions thereof and antibodies thereto for diagnosis and treatment of cell proliferative disorders, particularly cancers of the colon, breast, ovary, uterus, prostate, adrenal gland, and thyroid, and thyroid follicular adenoma and thyroid lymphocytic thyroiditis. The invention additionally provides expression vectors and host cells for the production of the proteins and transgenic model systems.

Abstract: The identification and characterisation of human and rat Islet-Brain 1 (IB1) is disclosed, a transcriptional activator that is involved in the control of the GLUT2 and insulin genes by interacting with homologous cis-regulatory elements of the GLUT2 and insulin promoters. The rat IB1 cDNA encodes a 714 amino acid protein and the human IB1 cDNA a 711 amino acid protein. The use of IB1 polypeptides, nucleic acid, agonists and antagonists in the treatment or diagnosis of diabetes, neurological diseases such as dementia and/or parkinsonism, the inhibition/promotion of apoptosis and cancer is disclosed.

Abstract: Nuclear matrix proteins (NMP) which are characterized by a defined expression in tissue, particularly prostate tissue, are provided. These NMPs are useful markers in diagnosing and monitoring the stage of malignancy of a cell and treating cell proliferative disorders associated with the NMP. Also provided are substantially purified polypeptides and nucleotide sequences encoding the NMPs of the invention.

Abstract: CARP-2 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing CARP-2 polypeptides and polynucleotides in diagnostic assays.

Abstract: Nuclear matrix proteins (NMP) which are characterized by a defined expression in tissue, particularly prostate tissue, are provided. These NMPs are useful markers in diagnosing and monitoring the stage of malignancy of a cell and treating cell proliferative disorders associated with the NMP. Also provided are substantially purified polypeptides and nucleotide sequences encoding the NMPs of the invention.

Abstract: The present invention relates to the immunization of animals and humans with trypanosome tubulin to protect against trypanosomes. More particularly, the present invention relates to a substantially pure tubulin preparation, which comprises a tubulin extract from Trypanosoma brucei which tubulin preparation can protect animals and humans against heterologous strains of different species of Trypanosoma.

Abstract: This invention relates to methods of screening for compounds capable of inducing apoptosis in certain tumor cells. The invention also relates to compounds identified by such methods. In addition, the invention relates to methods for the in vitro diagnosis of Xeroderma pigmentosum and compounds useful in these methods.

Abstract: The present invention relates to a method to determine predisposition to coagulation disorders, such as thrombosis, to a method for diagnosis of lupus, and therapeutical uses thereof in the treatment of coagulation disorders.

Abstract: A method for purifying cancer-specific Proliferating Cell Nuclear Antigen (csPCNA) is described, as well as an immunoassay based thereon.

Abstract: The present invention provides nucleic acids and amino acids for novel olfactory receptors as well as methods for identifying olfactory receptors. More specifically, the present invention provides nucleic acids and amino acids for novel olfactory receptors in Drosophila as well as methods of using the provided nucleic acids and amino acids. In addition, this invention provides methods of identifying ligands which bind to the novel olfactory receptors as well as a variety of methods for using the ligands so identified.

Abstract: The present invention provides a novel human integral membrane (TMP-1) and polynucleotides which identify and encode TMP-1. The invention also provides genetically engineered expression vectors and host cells comprising the nucleic acid sequences encoding TMP-1 and a method for producing TMP-1. The invention also provides for agonists, antibodies, or antagonists specifically binding TMP-1, and their use, in the prevention and treatment of diseases associated with expression of TMP-1. Additionally, the invention provides for the use of antisense molecules to polynucleotides encoding TMP-1 for the treatment of diseases associated with the expression of TMP-1. The invention also provides diagnostic assays which utilize the polynucleotide, or fragments or the complement thereof, and antibodies specifically binding TMP-1.

Abstract: The invention provides human RNA binding proteins (RNABP) and polynucleotides which identify and encode RNABP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating or preventing disorders associated with expression of RNABP.

Abstract: A new protein named Tankyrase II is described in this disclosure. Sequences for the human Tankyrase II cDNA and the protein translation product are provided. Also provided are species homologs, muteins, related nucleic acids, peptides, and drug screening assays. Tankyrase II interacts with telomere-associated proteins, thereby affecting telomerase activity and potentially telomere length. The materials and techniques provided in this disclosure allow Tankyrase II activity to be studied in vitro and manipulated inside cells—to the potential benefit of clinical conditions associated with a defect in telomerase activity, or the replicative capacity of affected cells.

Abstract: A serum-free composition comprises a conjugate of a DNA-binding protein, or a fragment thereof, and a polynucleotide. The composition is suitable for intramuscular administration, to treat disease.

Abstract: The present invention relates to peptides comprising at least one sequence selected from the group consisting of oligopeptide sequences of at least about 10 but not more than about 50 continuous amino acid residues in the amino acid sequence of the C-terminal acidic tail (ATS), which can render fusion partner proteins environmental stress resistant by binding thereto while conserving their intrinsic properties. Also, it relates to fusion proteins formed by binding the above peptides to fusion partner proteins, nucleotide sequences encoding said fusion proteins, recombinant vectors comprising said nucleotide sequences, and cells transformed or transfected with said recombinant vectors. In addition, it relates to processes for producing the above environmental stress resistance conferring peptides or environmental stress resistant fusion proteins by chemical synthesis or genetic recombination.

Abstract: A human gene termed CIF130 and its expression products can alter the spatial or temporal patterns of mitosis or cell cycle progression of a human cell. Methods of treating disorders involving alterations in the regulation of mitosis or cell cycle progression utilize the gene and its expression product. Genes whose expression is dependent upon CIF130 expression can be identified.

Abstract: This invention pertains to the discovery that DPR-1 encodes a putative nuclear hormone receptor (NHR) that, based on gene reporter studies, is expressed in the endoderm throughout the life of the worm. NHR family members are transcriptional regulators that are activated when bound to their small lipophilic ligands such as steroids. While some NHRs are localized to the nucleus, others are cytoplasmic in the absence of ligand and translocate to the nucleus upon ligand binding. Once in the nucleus, they bind target sequences and regulate gene expression.

Abstract: A process is described for the recombinant production of ribonucleoproteins in prokaryotic cells.

Abstract: A transcription factor, which is a transcriptional activator or a transcriptional repressor, comprising a DNA-binding domain and a transcriptional activator or repressor domain, and optionally a regulatory domain for ligand-dependent DNA binding and/or transcriptional activation or repression by the transcription factor, wherein the transcription factor is chimeric, comprising a HNF1 polypeptide DNA-binding domain and a transcriptional activator or repressor domain of a different polypeptide, with the proviso that where the transcription factor is a transcriptional activator comprising a transcriptional activator domain the transcription factor does not comprise a regulatory domain which binds AcylHSL or an analogue thereof whereby upon AcylHSL binding DNA binding function of the DNA-binding domain is activated. A transcriptional activator comprises a human HNF1 polypeptide DNA-binding domain, a human estrogen receptor alpha regulatory domain containing a G521R mutation, and a human p65 activation domain.

Abstract: The invention provides a human microtubule-associated protein (HMAP) and polynucleotides which identify and encode HMAP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for treating or preventing disorders associated with expression of HMAP.

Abstract: The present invention provides a human microtubule-associated protein (hLC3) and the polynucleotides which identify and encode hLC3. The invention also provides genetically engineered expression vectors, host cells, and a method for producing hLC3. The invention also provides hLC3 as well as agonists, antibodies, and antagonists of hLC3, and the use thereof for the prevention and treatment of diseases associated with the expression of hLC3. Additionally, the invention provides for the use of antisense molecules to polynucleotides encoding hLC3 for the treatment of diseases associated with the expression of hLC3. The invention also provides diagnostic assays which utilize the polynucleotide, or fragments or the complement thereof, and antibodies specifically binding hLC3.

Abstract: The invention provides isolated nucleic acids that encode human NAC-1, and fragments thereof, vectors for propagating and expressing human NAC-1 nucleic acids, host cells comprising the nucleic acids and vectors of the present invention, proteins, protein fragments, and protein fusions of the novel human NAC-1 isoforms, and antibodies thereto. The invention further provides transgenic cells and non-human organisms comprising human NAC-1 nucleic acids, and transgenic cells and non-human organisms with targeted disruption of the endogenous orthologue of the human NAC-1 gene. The invention further provides pharmaceutical formulations of the nucleic acids, proteins, and antibodies of the present invention, and diagnostic, investigational, and therapeutic methods based on the human NAC-1 nucleic acids, proteins, and antibodies of the present invention.

Abstract: The invention includes antibiotic pharmaceutical compositions comprising eukaryotic histone H1 protein and methods of using eukaryotic histone H1 protein to kill or to inhibit the growth of microorganisms, including, but not limited to, human pathogenic bacteria. The invention further includes a eukaryotic histone H1-containing animal feed and methods of improving growth of an animal by supplying the feed to the animal. The invention still further includes a kit comprising a eukaryotic histone H1-containing antibiotic pharmaceutical composition and an instructional material which describes the use of the composition. In addition, the invention includes a vaccine comprising a eukaryotic histone H1 protein and a method of vaccinating an animal using the vaccine.

Abstract: The invention provides human nuclear hormone receptors (NHREC) and polynucleotides which identify and encode NHREC. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. This invention also provides methods for diagnosing, treating or preventing disorders associated with aberrant expression of NHREC.

Abstract: A database search using the sequence of transcriptional regulator “RING3” having a bromodomain identified an EST sequence that is highly homologous with RING3. Using primers prepared based on the EST sequence, a gene encoding a novel transcriptional regulator having a bromodomain has been successfully isolated from a human testis cDNA library by polymerase chain reactions. The results of analysis of the isolated gene revealed that this gene is expressed strongly in testis cells with a potent proliferative ability. The use of the above transcriptional regulator and its gene enables screening candidate compounds for factors interacting with the transcriptional regulator or drugs controlling the activity of the regulator.

Abstract: Heterodimerization is a common paradigm among eucaryotic transcription factors, though it remains unclear how individual monomers contribute to the overall transcriptional activities of the complex. The 9-cis retinoic acid receptor (RXR) serves as a common heterodimerization partner for several nuclear receptors including the thyroid hormone (T3R), retinoic acid (RAR) and vitamin D receptors. A strategy has been devised to examine the transcriptional properties of each receptor individually or when tethered to a heterodimeric partner. It has been found that the intrinsic activity of RXR is masked in RXR-T3R and RXR-RAR heterodimers. In contrast, a novel RXR-Nurrl heterodimer described herein is highly responsive to RXR ligands, suggesting that different partners exert unique allosteric control over the RXR response.

Abstract: The present invention relates to a polynucleotide comprising a ubiquitous chromatin opening element (UCOE) which is not derived from 13. The polynucleotide of any one of claims 1 to 7, wherein the UCOE comprises the sequence of FIG. 20 between nucleotides 1 to 7627 or a functional homologue or fragment thereof. an LCR. The present invention also relates to a vector comprising the polynucleotide sequence, a host cell comprising the vector, use of the polynucleotide, vector or host cell in therapy and in an assay, and a method of identifying UCOEs. The UCOE opens chromatin or maintains chromatin in an open state and facilitates reproducible expression of an operably-linked gene in cells of at least two different tissue types.

Abstract: The invention relates to recombinantly produced human histone-1 subtypes and to their use for therapeutic purposes.

Abstract: The present invention is directed to novel polypeptides having homology to certain human uncoupling proteins (“UCPs”) and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention, and methods for producing the polypeptides of the present invention.

Abstract: This invention relates to isolated nucleic acid fragments encoding polypeptides involved in post-transcriptional gene silencing. The invention also relates to construction of a recombinant DNA construct encoding all or a portion of the polypeptide involved in post-transcriptional gene silencing, in sense or antisense orientation, wherein expression of the recombinant DNA construct results in production of altered levels in a transformed host cell of the the polypeptide involved in post-transcriptional gene silencing.

Abstract: This invention relates to a novel bacterial ribonucleoprotein complex and the component parts thereof. More specifically, this invention relates to SRP isolated from Staphylococcus aureus and the use of SRP or components thereof in screens for the identification of antimicrobial compounds and to the use of such compounds in therapy.

Abstract: This invention provides purified telomerase and methods of purifying it. The methods involve the use of several sequential steps, including the use of matrices that bind molecules bearing negative charges, matrices that bind molecules bearing positive charges, intermediate-selectivity matrices, methods that separate molecules based on their size, shape, or buoyant density, and by affinity purification.

Abstract: The present invention relates to novel soluble combinatorial libraries, comprising a soluble phase in solution attached to a core molecule, and allowing the improved high-yield and efficient production of soluble combinatorial libraries. Some specific examples of the soluble combinatorial libraries claimed herein comprise one or more of the following: amino acids, &agr;-azetide amino acids, triazine dione molecules, &ggr;-lactamtide molecules, &dgr;-lactamthiotide molecules, &bgr;-lactam nucleus containing molecules, lycoramine alkaloid nucleus containing molecules, and &bgr;-blocker nucleus molecules. Further, a split synthesis technique for generating libraries of combinatorial molecules employs a biphasic macromolecular support which is soluble during the pooling, splitting, and coupling steps but which is insoluble during the washing step. The use of a biphasic macromolecular support in its soluble phase significantly enhances the efficiency and performance of the pooling, splitting, and coupling steps.

Abstract: This invention provides a novel G protein-coupled receptor, i.e. a purinoceptor (P2Y receptor), and a gene thereof. It further provides a novel method for screening, identifying or characterizing a ligand and agonist or antagonist.

Abstract: Zinc finger proteins of the Cys2His2 type represent a class of malleable DNA binding proteins which may be selected to bind diverse sequences. Typically, zinc finger proteins containing three zinc finger domains, like the murine transcription factor Zif268 and the human transcription factor Sp1, bind nine contiguous base pairs (bp). To create a class of proteins which would be generally applicable to target unique sites within complex genomes, the present invention provides a polypeptide linker that fuses two three-finger proteins. Two six-fingered proteins were created and demonstrated to bind 18 contiguous bp of DNA in a sequence specific fashion. Expression of these proteins as fusions to activation or repression domains allows transcription to be specifically up or down modulated within cells. Polydactyl zinc finger proteins are broadly applicable as genome-specific transcriptional switches in gene therapy strategies and the development of novel transgenic plants and animals.

Abstract: The invention provides isolated nucleic acid and amino acid sequences of KinI-3, antibodies to KinI-3, methods of screening for KinI-3 modulators using biologically active KinI-3, and kits for screening for KinI-3 modulators.

Abstract: The present invention provides novel human cell division cycle proteins (collectively called HCDC) and polynucleotides which identify and encode HCDC. The invention also provides genetically engineered expression vectors and host cells comprising the nucleic acid sequences encoding HCDC. The invention also provides pharmaceutical compositions containing HCDC or antagonists to HCDC, and in the use of these compositions for the treatment of diseases associated with the expression of HCDC. Additionally, the invention provides for the use of antisense molecules to polynucleotides encoding HCDC for the treatment of diseases associated with the expression of HCDC. The invention also provides diagnostic assays which utilize the polynucleotide, or fragments or the complement thereof, to hybridize to the genomic sequence or transcripts of polynucleotides encoding HCDC or anti-HCDC antibodies which specifically bind to HCDC.

Abstract: The invention provides isolated nucleic acids molecules, designated SMRTe nucleic acid molecules, which encode proteins involved in nuclear receptor mediated activities. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing SMRTe nucleic acid molecules, host cells into which the expression vectors have been introduced, methods for identifying compounds that modulate SMRTe activity, and nonhuman transgenic animals in which a SMRTe gene has been introduced or disrupted. The invention still further provides isolated SMRTe proteins, fusion proteins, antigenic peptides, and anti-SMRTe antibodies. Diagnostic methods utilizing compositions of the invention are also provided.

Abstract: New protein-polycation conjugates which are capable of forming soluble complexes with nucleic acids contain as their protein component an antibody directed against a cell surface protein, with the ability to bind to the cell surface protein so that the complexes formed are absorbed into cells which express the cell surface protein and are expressed therein. Complexes for use in pharmaceutical preparations contain a therapeutically or gene therapeutically active nucleic acid.

Abstract: The present invention provides polynucleotides which identify and encode a novel human nm23-like protein (H-nm23). The invention provides for genetically engineered expression vectors and host cells comprising the nucleic acid sequence encoding H-nm23 and for a method for producing the protein. The invention also provides for the use of substantially purified H-nm23 for the for the treatment of diseases associated with the expression of H-nm23. The invention also describes diagnostic assays which utilize diagnostic compositions comprising the polynucleotides which hybridize with naturally occurring sequences encoding H-nm23 and antibodies which specifically bind to the protein.

Abstract: The present invention includes peptides derived from nucleosomal histone proteins which are useful for delaying the onset and progression of systemic lupus erythematosus (i.e. lupus or SLE). The peptides of the invention span the histone proteins (i.e. H1, H2A, H2B, H3, and H4). The invention additionally encompasses isolated nucleic acids which encode these histone peptides as well as pharmaceutical compositions which comprise one or more of a histone peptide. Further, the invention provides kits which comprise one or more histone peptides or isolated nucleic acids encoding histone peptides and an instructional material. The invention also provides methods of using these compositions and analogs of histone peptides to inhibit an immune response and associated inflammation in an animal and to treat disorders in an animal which are related to the production of autoantibodies and complications thereof, such as inflammatory diseases, autoimmune disorders, and nephritis.

Abstract: The present invention relates to novel human Prt1 (hPrt1) and eIF4G-like (p97) proteins which are involved in eukaryotic transcription In particular, isolated nucleic acid molecules are provided encoding the human hPrt1 and p97 proteins. hPrt1 and p97 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of hPrt1 and p97 activity. Also provided are therapeutic methods for treating disease states associated with the hPrt1 and p97 proteins.

Abstract: The present invention provides recombinant nucleic acid molecules encoding a chimeric transactivator protein including a DNA binding domain of a DNA binding protein and a protein domain capable of transcriptional activation. The present invention also provides recombinant viral and non-viral vectors that are able to infect and/or transfect and sustain expression of a biologically active chimeric transactivator proteins in mammalian cells. Also provided are host cell lines and non-human transgenic animals capable of expressing biologically active chimeric transactivator proteins. In another aspect, compositions and methods for treating or preventing ischemic damage associated with hypoxia-related disorders are provided.

Abstract: The invention provides human polynucleotide sequences that encode transcription factor polypeptides that are termed ALF and SALF, and an alternative C-terminal sequence. The invention includes ALF, SALF and alternative C-terminus polypeptides, peptides, fusion proteins, expression vectors, agonists, antagonists, host cells that overexpress these polypeptides, including transgenic animals, and recombinant knock-out animals that cannot express the relevant RNAs and polypeptides. The invention also provides methods for the detection, diagnosis, screening, and monitoring disorders related to inappropriate expression, production, or activity of ALF and SALF, and provides methods to increase or decrease gene expression with respect to treating disorders related to inappropriate or ineffectual patterns of gene expression.

Abstract: HNF-4 (hepatocyte nuclear factor 4) is a protein enriched in liver extracts that binds to sites required for the transcription of the transthyretin (TTR) and apolipoprotein CIII (apoCIII) genes (Costa et al., 1989; Costa et al., 1990; Leff et al., 1989). We have purified HNF-4 protein (54 kD) and isolated a cDNA clone encoding the protein. HNF-4 is a member of the steroid hormone receptor superfamily with an unusual amino acid in the conserved “knuckle” of the first zinc finger (DGCKG). This and the fact that HNF-4 does not bind significantly to estrogen, thyroid hormone or glucocorticoid response elements indicate that HNF-4 may represent a new subfamily. HNF-4 binds to its recognition site as a dimer and activates transcription in a sequence-specific fashion in nonhepatic (HeLa) cells. HNF-4 mRNA is present in kidney and intestine as well as liver but is absent in other tissues.

Abstract: The present invention relates to a dermatomyositis-specific auto-antigen, a DNA encoding it and a process for the preparation thereof as well as its use.

Abstract: The present invention provides mutant proteins of steroid hormone receptors. These mutant proteins are useful in methods of distinguishing a steroid hormone receptor antagonist from a steroid hormone receptor agonist. The present invention also provides plasmids containing mutated steroid hormone receptor proteins and cells transfected with those plasmids. In addition, the present invention provides methods for determining whether a compound is a steroid hormone receptor antagonist or agonist. Also, the present invention provides methods of determining endogenous ligands for steroid hormone receptors. The invention further provides a molecular switch protein for regulating expression in gene therapy.

Abstract: This invention provides a method of modulating translation termination efficiency of mRNA and/or promoting degradation of abberant transcripts. Also, this invention provides a method of screening for a drug active involved in enhancing translation termination and a method for identifying a disease state involving defective the protein complex. This invention provides a purified complex comprising an amount of a human Upf1p protein, a peptidyl eucaryotic release factor 1 (eRF1) and a peptidyl eucaryotic release factor 3 (eRF3) effective to modulate translation termination. Further, this invention provides an expression vector which comprises a nucleic acid encoding a human Upf1p protein, a peptidyl eucaryotic release factor 1 (eRF1) and a peptidyl eucaryotic release factor 3 (eRF3) operably linked to a regulatory element.

Abstract: A purified recombinant thermostable DNA polymerase polymerase which exhibits at least about 80% activity at salt concentations of 50 mM and greater, at least about 70% activity at salt concentrations of 25 mM and greater, and having a processivity of about 30 nucleotides per binding event. An isolated nucleic acid that encodes the thermostable DNA polymerase, as well as a recombinant DNA vector comprising the nucleic acid and a recombinant host cell transformed with the vector, are also disclosed. A method of sequencing DNA using the DNA polymerase as well as a kit for sequencing DNA is also disclosed.