Abstract: A soluble immunosuppressive factor present in serum derived from tumor-bearing mammals, is associated with changes in TCR protein subunit levels, T lymphocyte signal transduction pathway proteins. These changes provide a method of determining the level of immunosuppression in a mammal by determining the level of expression of at least one selected TCR subunit protein, a protein in the T lymphocyte signal transduction pathway, or of the NF-.kappa.B/rel family and comparing the level and pattern to that found in non-immunosuppressed individuals. The method is useful to identify patients having T lymphocytes capable of activation for immunotherapy and for identifying agents which cause or reverse immunosuppression. An isolated immunosuppressive factor associated with the level of expression of the proteins is useful for suppressing the immune response, for example, in organ transplantation.

Abstract: The present invention relates generally to intracellular receptor recognition proteins or factors, termed Signal Transducers and Activators of Transcription (STAT), to methods and compositions utilizing such factors, and to the antibodies reactive toward them, in assays and for diagnosing, preventing and/or treating cellular debilitation, derangement or dysfunction. More particularly, the present invention relates to particular functional domains of molecules that exhibit both receptor recognition and message delivery via DNA binding in receptor-ligand specific manner, i.e., that directly participate both in the interaction with the ligand-bound receptor at the cell surface and in the activity of transcription in the nucleus as a DNA binding protein. The invention likewise relates to the antibodies and other entities that are specific to the functional domain of a STAT protein and that would thereby selectively modulate its activity.

Abstract: Three mammalian are disclosed which are useful in the diagnosis and prognosis of tumors of lymphoid and epithelial origin. The three proteins are immunologically related to each other. The level of expression of the proteins correlates with the malignant potential of lymphoid and epithelial tumors. In addition, in some cases the subcellular location of the proteins is indicative of malignant potential. Antibodies reactive with the proteins are disclosed as diagnostic tools, as are nucleic acid probes and primers for quantitating the messenger RNAs encoding the proteins. Methods for preparing and purifying the proteins are also taught.

Abstract: The present invention is directed to protamine-reactive, IgM antibodies, and their uses in prognosis, diagnosis, and therapy. In a specific embodiment, the invention relates to low affinity binding, protamine-reactive serum IgM antibodies. In particular, such antibodies can recognize a sequence comprising four arginyl residues, including a triplet, within a six amino acid residue sequence. Such antibodies may be natural antibodies (i.e., not induced). A low affinity subset of serum protamine-reactive IgM antibodies may be assayed for prognosis or diagnosis of AIDS. Such antibodies are detectable in sera of normal subjects and HIV-infected individuals who subsequently exhibit a significant period of latency, but are absent or deficient in sera of individuals diagnosed with AIDS and sera of HIV infected individuals, who though asymptomatic at the time of the sampling, proceed to AIDS within a relatively short time.

Abstract: The protein DP-1, part of the DP-1/E2F-1 transcription factor complex, as well as DP-2 and DP-3 has its phosphorylation level regulated during cell cycle progression. This finding allows assays to be based on changes in phosphorylation of DP proteins, in particular for agents which may affect the phosphorylation state of DP. DP-1 has been found to have a greater affinity to DNA when in a hypophosphorylated state. Antibodies that recognize phosphorylation sites on DP-1 are also disclosed.

Abstract: The invention features a novel recombinant polypeptide that transactivates the somatostatin promoter, the polypeptide being present in pancreatic duct cells and not present in pancreatic .alpha.-cells, the polypeptide being encoded by a gene which encodes a protein on the order of 31 kd.

Abstract: The present invention provides polynucleotides which identify and encode a novel human nucleic acid binding protein (NABP). The invention provides for genetically engineered expression vectors and host cells comprising the nucleic acid sequences encoding NABP. The invention also provides for the use of substantially purified NABP or its antagonists, in pharmaceutical compositions for the treatment of diseases associated with the expression of NABP. Additionally, the invention provides for the use of antisense molecules to NABP in pharmaceutical compositions for treatment of diseases associated with the expression of NABP. The invention also describes diagnostic assays which utilize diagnostic compositions comprising the polynucleotide, fragments or the complement thereof, which hybridize with the genomic sequence or the transcript of polynucleotides encoding NABP or anti-NABP antibodies which specifically bind to NABP.

Abstract: A modified p53 protein or peptide having DNA binding in which amino acid residue 284 of a p53 protein or protein fragment is changed to Arginine or Lysine, is described. Also described are nucleotide sequences encoding the modified protein and vectors capable of expressing it.

Abstract: A cell division mechanism controlling protein which is not expressed during interphase but is expressed in the nucleus after entering into the cell cycle of a mammalian cell, fragments thereof, as well as DNAs coding for said protein or fragments thereof, as well as antibodies against said protein or fragment thereof.

Abstract: An assay for screening test compounds to indentify agents which modulate the binding of an E6-BP polypeptide with a papilloma virus E6 protein. The assay includes combining, as a cell-free system, an E6-binding protein or fragment thereof which binds to the E6 protein, and a test compound, and detecting the formation of a complex which includes the E6 protein and the E6-binding protein. A change in the formation of the complex in the presence of the test compound is indicative of an agent that modulates interaction between an E6 and an E6-binding protein.

Abstract: Phospho-specific antibodies which recognize the phosphorylated forms of cAMP-responsive transcription factors are provided.

Abstract: The present invention provides novel fusion proteins comprising cyclins and CDKs. A preferred embodiment of the invention provides fusion proteins comprising human cyclin D1 and human CDK4. The fusion proteins of the invention optionally contain modifications, which facilitate their purification. Addition of histidine residues to selected constructs allows purification via immobilized metal affinity chromatography. Antigenic determinants allowing monoclonal antibody-based affinity chromatography purification are provided in selected embodiments of the invention. Protease cleavage sites are incorporated in selected constructs to allow cleavage of the regions incorporated in the cyclin-CDK fusion proteins for purification. Additional modifications which facilitate purification include strepavadin binding domains and antigenic determinants for antibody affinity chromatography.

Abstract: An autoantigen identified as HP-8 which is related to systemic lupus erythematosus. The HP-8 antigen is expressed by a gene which was identified by immunoscreening of human placental cDNA GT11 expression library with the monoclonal antibody 3E10. The 3E10 antibody is a low-affinity anti-double-stranded DNA autoantibody derived from the MRL murine models for human systemic lupus erythematosus.

Abstract: Solid phase reagents having immobilized thereon novel single-chain Fv antibodies specific to SS-A/Ro autoantigens have been developed for use in immunoassays to detect the presence or amount of autoantibodies to such autoantigens in a test sample. The solid phase reagents can also be used to purify autoantigen. Diagnostic test kits which contain these single-chain Fv antibodies specific to SS-A/Ro autoantigen useful in immunoassays are also described.

Abstract: The invention relates to a system for transporting nucleic acids into the cell, which is effected by receptor-mediated endocytosis. Using a transferrin-polycation conjugate, a complex can be formed with the polyanionic nucleic acid. This complex is bound to the transferrin receptor, which is highly regulated in growing cells, and absorbed into the cell. Suitable nucleic acids include those which inhibit specific genes or the RNA function, such as antisense oligonucleotides or ribozymes or the genes coding for them. The invention further relates to a process for introducing nucleic acids into the cells, transferrin-polycation/nucleic acid complexes and pharmaceutical preparations containing them.

Abstract: Described is a polypeptide comprising one or more zinc fingers. The polypeptide binds to new polynucleotide subsites with high affinity and consequently has a binding specificity that differs from wild type zinc finger proteins. The binding occurs through contacts between certain amino acid residues of the zinc fingers and the nucleic acids of the subsites. The polypeptide sequence of at least one zinc finger differs from wild type zinc fingers, and the difference involves at least one amino acid residue that contacts the bases of the polynucleotide during binding.

Abstract: Disclosed are genetic sequences and their encoded amino acid sequences for two interior nuclear matrix proteins useful as markers of malignant cell types. Primary and secondary structure analysis of the proteins is presented as well as means for their recombinant production, and compositions and methods for the use of these markers in clinical assays and cancer therapies.

Abstract: Disclosed are DNA sequences encoding novel DNA binding proteins implicated in regulation of early stages of cell growth. Illustratively provided are human and mouse origin DNA sequences encoding early growth regulatory ("Egr") proteins which include "zinc finger" regions of the type involved in DNA binding. Also disclosed is a detailed analysis of the structure and function of the early growth regulatory protein, Egr-1, delineating independent and modular activation, repression, DNA-binding, and nuclear localization activities. Also disclosed are immunological methods and materials for detection of Egr proteins and hybridization methods and materials for detection and quantification of Egr protein related nucleic acids.

Abstract: This invention relates to the isolation, identification and sequencing of a cancer associated protein, preparation of hybridization probes therefrom, preparation of antibodies thereto, and methods of cancer risk assessment and diagnosis.

Abstract: The present invention is based on the identification and sequence determination of a novel gene, ALK, which is fused to the gene encoding nucleophosmin (NPM) in translocations present in t(2;5) lymphoma cells. Based on homologies to other proteins, the amino acid sequence of the polypeptide encoded by the ALK (Anaplastic Lymphoma Kinase) gene is a membrane-spanning protein tyrosine kinase (PTK)/receptor. Antibodies to the ALK PTK/receptor and methods utilizing such antibodies are described, as are methods of using the ALK gene to isolate ligands for the ALK PTK/receptor.

Abstract: We have discovered a nuclear protein in normal human cells, "retinoblastoma-associated protein 1" ("RBAP-1"), also known as E2F-1, that binds directly to the retinoblastoma protein pocket of the underphosphorylated form of the retinoblastoma protein ("RB") and does not bind to phosphorylated RB or to RB with inactivating mutations. The translated RBAP-1 sequence does not resemble other proteins whose sequences are known, and RBAP-1 does not contain a sequence homologous to the transforming element common to viral proteins that bind to the RB pocket. RBAP-1 and the E2F transcription activity have similar DNA-binding specificities and can bind to at least some of the same proteins, such as RB and E4.

Abstract: Three mammalian are disclosed which are useful in the diagnosis and prognosis of tumors of lymphoid and epithelial origin. The three proteins are immunologically related to each other. The level of expression of the proteins correlates with the malignant potential of lymphoid and epithelial tumors. In addition, in some cases the subcellular location of the proteins is indicative of malignant potential. Antibodies reactive with the proteins are disclosed as diagnostic tools, as are nucleic acid probes and primers for quantitating the messenger RNAs encoding the proteins. Methods for preparing and purifying the proteins are also taught.

Abstract: The present invention provides a process of transfecting a cell with a polynucleotide mixed with one or more amphipathic compounds and an effective amount of a DNA-binding protein. Exemplary and preferred DNA-binding proteins are H1, H2A, and H2B. Exemplary and preferred amphipathic compounds are cationic amphipathic compounds.

Abstract: Materials and methods are described for identifying signal transducing molecules which activate promoters, such as the human c-fos proto-oncogene promoter, as well as antagonists of such molecules. Also described are human c-fos promoter activating proteins, and in particular novel proteins, designated CROC-1 protein and CROC-4 protein, nucleic acids encoding said proteins, and mammalian cells transfected with vectors containing such nucleic acids.

Abstract: The subject invention provides for nucleotide sequences encoding polypeptide p62 and derivatives thereof. Another aspect of the subject invention also provides for methods of purifying p62 and derivatives thereof from cells naturally producing p62 and from cells genetically modified so as to produce p62. The subject invention also provides for methods of assaying tyrosine kinase activity by means of measuring the phosphorylation of p62 and p62 derivatives. Measurement of p62/p62 derivative phosphorylation may be used to determine whether or not a call is cancerous.

Abstract: The present invention provides p53 proteins with altered tetramerization domains that retain wild-type p53 function, and the ability to form tetramers and have at least one of the following characteristics: (1) do not hetero-oligomerize with wild-type p53 or tumor-derived p53 mutants, and (2) restricted DNA binding specificity from an alteration in the way that the tetramerization domain orients the DNA binding domains of a p53 tetramer relative to one another. The invention also provides nucleic acids encoding the above proteins and methods of enhancing the cellular response to DNA damaging agents, treating diseases characterized by abnormal cell proliferation, and inducing immune tolerance to facilitate transplants and treatment of autoimmune disease, by administration of proteins of the invention or nucleic acid sequences encoding the proteins of the invention.

Abstract: A method of screening a cell for the onset of senescence or a senescent state therein comprises detecting a p21-E2F complex in the cell, an elevation in the complex as compared to a normal cell indicating the onset of senescence or a senescent state in the cell. Isolated complexes comprised of p21 and E2F are also disclosed. The complexes stably bind to DNA and are useful, among other things, for binding DNA.

Abstract: Disclosed are genetic sequences and their encoded amino acid sequences for two interior nuclear matrix proteins useful as markers of malignant cell types. Primary and secondary structure analysis of the proteins is presented as well as means for their recombinant production, and compositions and methods for the use of these markers in clinical assays and cancer therapies.

Abstract: 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.

Abstract: Viruses or cells are targeted for selective internalization into a target in vive. A molecule Specific for a receptor on the surface of the target cell is introduced onto the surface of the virus or cell. The modified virus or cell binds the receptor in vive and is internalized by the target cell. The method provides vectors for selective delivery of nucleic acids to specific cell types in vivo and a means to alter the tropism of an infectious agent.

Abstract: Compositions including a polypeptide or nucleic acid sequence encoding a polypeptide that binds TAR DNA (particularly the region -18 to +28 of HIV-LTR DNA) and that does not bind to TAR RNA (particularly the region +1 to +80 of the TAR RNA) are disclosed. The cellular binding protein TDP-43 including the polypeptide has an estimated molecular weight of between about 40 kD and 46 kD as determined by SDS polyacrylamide gel electrophoresis. Fusion proteins that include the entire cellular binding protein TDP-43 or fragments thereof are also described. The cellular binding protein, peptide fragments and nucleic acid sequences encoding them, repress HIV gene expression. Methods for preparing the cellular binding protein from cells as recombinant proteins with recombinant host cells are also disclosed. Antibodies to the TDP-43 cellular binding protein are also described. The isolated nucleic acid sequences of the protein and its fragments are described in the construction of retroviral vectors.

Abstract: Disclosed are genetic sequences and their encoded amino acid sequences for two interior nuclear matrix proteins useful as markers of malignant cell types. Primary and secondary structure analysis of the proteins is presented as well as means for their recombinant production, and compositions and methods for the use of these markers in clinical assays and cancer therapies.

Abstract: The present invention relates to the PUR protein, nucleotide sequences and expression vectors encoding PUR, and to methods for inhibiting PUR activity. Inhibitors of PUR activity may be used to treat hyperproliferative diseases such as cancer.

Abstract: Disclosed are methods of identifying compounds which inhibit transcription activation by CIITA and thus inhibit MHC class II gene expression. Such compounds can affect the induction of an immune response. The methods employ, independently, the activation and interactions domains of CIITA. The methods also employ the activation and interaction domains of isotype-specific CIITA proteins, allowing for the identification of compounds which are isotype-specific inhibitors of transcription and which are useful for selectively affecting the immune system.

Abstract: Method for identifying and isolating variant T4 DNA polymerase by isolating and selecting for T4 strains having variant DNA polymerase defective in DNA replication, and at least one additional mutation which corrects or compensates for said defect in DNA replication; identifying the additional mutation(s) and introducing the mutation(s) into T4 phage or T4 DNA polymerase expression vectors.

Abstract: The 5-terminal partially nucleotide sequence of each clone of a human fetal lung tissue cDNA library was determined. A clone having a novel sequence including a sequence homologous to that of the transcriptional control protein of a yeast was selected from among the above clones and its whole nucleotide structure was determined. It was confirmed that the protein encoded by the gene of the clone was a novel human transcriptional control protein (RPDL protein). Further, an expression vector for expressing the protein and a transformant obtained by transforming with such an expression vector can also be prepared.

Abstract: The present invention provides a novel human protein, SATB1, that binds matrix/scaffold-associating DNA regions (MARs). The novel human protein, predominantly expressed in the thymus, has an approximate molecular weight of about 85.9 kD. The SATB1 cDNA encodes a 763 amino acid sequence protein that is capable of binding to special AT rich sequences (ATC sequences). The invention further provides antibodies specifically reactive with such protein. Isolated nucleic acids encoding the novel MAR-binding protein are also provided, as well as vectors containing the nucleic acids and recombinant host cells transformed with such vectors. The invention further provides methods of detecting such nucleic acids by contacting a sample with a nucleic acid probe having a nucleotide sequence capable of hybridizing with the isolated nucleic acids of the present invention. Such probes can correspond to the ATC sequences.

Abstract: The present invention provides a bcl-2 gene inhibitory element (BIE), which can inhibit expression of a gene in position-dependent and orientation-dependent manner. The invention provides, for example, BIE-1, having the nucleotide sequence 5'-CAAGAATGCAA-3' (SEQ ID NO: 1), which acts in an orientation-dependent and position-dependent manner to down-regulate the expression of the bcl-2 gene. The invention also provides a BIE binding factor (BBF), which is a cellular factor that can bind to a BIE. The invention provides, for example, BBF-A, which binds to BIE-1, including a nucleic acid sequence (SEQ ID NO: 8) encoding a portion of the amino acid sequence (SEQ ID NO: 9) of BBF-A. The invention further provides an antibody that specifically binds BBF-A. The invention also provides screening assays for identifying agents that can increase or decrease the binding of a BBF to a BIE, modulate the expression of a nucleic acid molecule linked to a BIE or modulate apoptosis in a cell.

Abstract: The present invention provides a substantially purified protein, p114-MBP, which has an apparent molecular mass of about 114 kDa and specifically associates with a matrix attachment region DNA sequence context (MAR). p114-MBP is characterized, in part, by having substantial MAR binding activity in malignant tumor tissue but not in a corresponding non-cancerous tissue. The invention also provides a method of detecting the presence of malignant tumor tissue in a cell sample suspected of containing malignant tumor tissue by contacting the sample with a MAR, under conditions that allow the specific association of the MAR with p114-MBP, and detecting such specific association, which indicates the presence of malignant tumor tissue in the cell sample.

Abstract: The present invention relates to an improved composition for hybridizing polynucleotides with complementary nucleic acid sequences. Specifically, it relates to a composition for of increasing the specificity of a polynucleotide hybridization reaction in the presence of single-stranded nucleic acid binding protein.

Abstract: The present invention provides recombinant proteins having the hormone-binding and/or transcription-activating characteristics of a mineralocorticoid receptor. The invention also provides proteins expressed from recombinant DNA encoding a naturally occurring receptor having the hormone-binding and/or transcription-activating characteristics of a mineralocorticoid receptor.

Abstract: Hybrid regulatory proteins are provided which contain amino acid sequences that are susceptible to cleavage by specific proteolytic enzymes. When acted upon by such enzymes, the hybrid regulatory proteins are rendered substantially less active, thereby altering the rate of production of products of indicator genes that are controlled by the regulatory proteins. Also provided are DNAs encoding such regulatory proteins, recombinant vectors and transformed eukaryotic cells containing such DNAs, and methods for identifying inhibitors of the specific proteolytic enzymes.

Abstract: A conjugate of an antiviral nucleoside with a lactosaminated human albumin (L-HSA) and its method of preparation is described. The method of preparation involves the reaction of an antiviral phosphorylated nucleoside in the form of an imidizolide with L-HSA at a pH above 7.5 and running the reaction until the desired molar ratio of drug to L-HSA is obtained.

Abstract: The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

Abstract: A 68 kDa a calmodulin-binding protein obtained from cytoplasmic or nuclear eukaryotic cell fractions, which is induced in hemopoietic factor-dependent cell lines by at least one of the following cytokines: granulocyte-macrophage colony stimulating factor, granulocyte colony stimulating factor, interleukin-3 or interleukin-6.

Abstract: A method for the identification of compounds as inhibitors of oncoprotein action is described. A compound is identified as an inhibitor of oncoprotein action based on its ability to modulate the transcription of a reporter gene. Transcription of the reporter gene is dependent upon the binding of a fusion oncoprotein to a specific DNA binding element positioned upstream of the reporter gene promoter. The fusion oncoprotein contains a transcriptional regulatory domain from an oncoprotein and a DNA binding domain from a different protein.

Abstract: Disclosed is a method for determining whether a first protein is capable of physically interacting with a second protein. The method involves: (a) providing a host cell which contains (i) a reporter gene operably linked to a protein binding site; (ii) a first fusion gene which expresses a first fusion protein, the first fusion protein including the first protein covalently bonded to a binding moiety which is capable of specifically binding to the protein binding site; and (iii) a second fusion gene which expresses a second fusion protein, the second fusion protein including the second protein covalently bonded to a weak gene activating moiety; and (b) measuring expression of the reporter gene as a measure of an interaction between the first and the second proteins. Such a determination facilitates the isolation of the gene encoding the interacting protein. Also disclosed herein is recombinant Cdi1 polypeptide, nucleic acid encoding the Cdi1 polypeptide, and uses thereof.

Abstract: Ribonucleoproteins and DNA-binding proteins related to the amino acid sequence corresponding at least to residues 92-202 and up to about residues 1 to about 240 of sequence (III), or of a modification of such sequences (III) having at least 35% homology with sequence (III) are disclosed.

Abstract: Since sodium dodecyl sulfate (SDS) binds tightly to proteins but not to DNA, the addition of potassium chloride (KCl) to SDS lysates of cells, nuclei or mitochondria results in the formation of an insoluble precipitate which includes all proteins and detergent-resistant DNA-protein complexes separated from free DNA in the supernatant. The amount of SDS-precipitable DNA represents a measure of crosslinked DNA-protein. This precipitation method is useful for determining or quantitating crosslinked DNA-protein formed in cells, nuclei or mitochondria of animals following their exposure to crosslinking agents such as chromate, nickel, cis-Pt (II) diammine dichloride and formaldehyde. The method is also useful for evaluating agents for their ability to induce covalent DNA-protein crosslinking.

Abstract: A biochemical procedure for identification and characterization of cells in a biopsy or sample of a body fluid. The method can be used to determine cell type, i.e. epidermal, neuronal; tissue of origin, i.e. breast tissue, liver tissue; and degree of abnormality. The procedure can also be used to make antibodies and hybridization probes to detect cell or tissue specific antigens and nuclear matrix associated nucleic acids in cellular material and body fluids.The procedure is based on the isolation and analysis of the components of a specific subcellular protein fraction referred to here as the "nuclear matrix". The nuclear matrix includes proteins and nuclear matrix associated DNA specific to different cell types. These proteins and nucleic acids are altered or new ones expressed as a result of viral infection, genetic defects or malignancy.