Abstract: The present invention concerns a novel human ubiquitin-conjugating enzyme which is implicated in the ubiquitin-mediated inactivation of cell-cycle regulatory proteins, partucularly p53. The present invention makes available diagnostic and therapeutic assays and reagents for detecting and treating transformed cells, such as may be useful in the detection of cancer. The present invention also provides reagents for altering the normal regulation cell proliferation in untransformed cells, such as by upregulating certain cell-cycle checkpoints, e.g. to protect normal cells against DNA damaging reagents.

Abstract: Processes and kits for simultaneously amplifying and sequencing nucleic acid molecules, and perfonning high throughput DNA sequencing are described.

Abstract: The present invention makes available an interaction trap system (hereinafter "ITS") which is derived using recombinantly engineered prokaryotic cells.

Abstract: The present invention concerns a novel paracrine signaling assay.

Abstract: The present invention relates to a substantially pure population of viable bile duct progenitor cells, and methods for isolating such cells. The present invention further concerns certain therapeutic uses for such progenitor cells, and their progeny.

Abstract: The present invention relates to the discovery that antisense nucleic acids complimentary to an E6AP gene can be used to regulate cellular p53 levels. In general the invention features E6AP antisense constructs which, by inhibiting E6AP activity, can modulate cellular p53 levels in both p53+ transformed cells and in normal cells. The invention also provides methods for treating papillomavirus (PV) induced condition, methods for regulating cellular p53 levels and methods for regulating cellular proliferation.

Abstract: Methods for determining the sequence of nucleic acids by cleaving the nucleic acid unilaterally from a first end with an exonuclease activity to sequentially release individual nucleotides, identifying each of the sequentially release nucleotides by mass spectrometry, and determining the sequence of the nucleic acid from the identified nucleotides are disclosed. The method is amenable to multiplexing for simulataneously determining more than one nuleic acid sequence.

Abstract: The present invention concerns the discovery that proteins encoded by a family of vertebrate genes, termed here hedgehog-related genes, comprise morphogenic signals produced by embryonic patterning centers, and are involved in the formation of ordered spatial arrangements of differentiated tissues in vertebrates. The present invention makes available compositions and methods that can be utilized, for example to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

Abstract: Invertebrate and vertebrate patched genes are provided, including the mouse and human patched genes, as well as methods for isolation of related genes, where the genes may be of different species or in the same family. Having the ability to regulate the expression of the patched gene, allows for the elucidation of embryonic development, cellular regulation associated with signal transduction by the patched gene, the identification of agonist and antagonist to signal transduction, identification of ligands for binding to patched, isolation of the ligands, and assaying for levels of transcription and expression of the patched gene.

Abstract: Assays for determining whether a subject has or is at risk for developing type II diabetes, which are based on detecting the presence or absence of alterations in the hepatic nuclear factor 1 (HNF-1) gene or protein of the subject are disclosed.

Abstract: Methods for identifying compounds, which modulate the bioactivity of human hepatic nuclear factor-1 (HNF-1), and which are therefore useful in treating type II diabetes are disclosed.

Abstract: The present invention relates to the discovery of a novel EPH receptor ligand, referred to hereinafter as "Elf-1", which protein has apparently broad involvement in the formation and maintenance of ordered spatial arrangements of differentiated tissues in vertebrates, and can be used to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

Abstract: The present invention concerns the discovery that proteins encoded by a family of vertebrate genes, termed here hedgehog-related genes, comprise morphogenic signals produced by embryonic patterning centers, and are involved in the formation of ordered spatial arrangements of differentiated tissues in vertebrates. The present invention makes available compositions and methods that can be utilized, for example to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

Abstract: The present invention makes available methods and reagents for novel manipulation of nucleic acids. As described herein, the present invention makes use of the ability of intronic sequences, such as derived from group I, group II, or nuclear pre-mRNA introns, to mediate specific cleavage and ligation of discontinuous nucleic acid molecules. For example, novel genes and gene products can be generated by admixing nucleic acid constructs which comprise exon nucleic acid sequences flanked by intron sequences that can direct trans-splicing of the exon sequences to each other. The flanking intronic sequences can, by intermolecular complementation, form a reactive complex which promotes the transesterification reactions necessary to cause the ligation of discontinuous nucleic acid sequences to one another, and thereby generate a recombinant gene comprising the ligated exons.

Abstract: The present invention makes available novel compounds useful for inhibiting kinases, phosphatases and SH2 domains, e.g., an interaction between a protein containing an SH2 domain and a phophotyrosine-containing polypeptide. In one embodiment, the present invention provides boronylphenyl analogs of phosphotyrosines which, in such forms as peptidomimetics, can be used to modulate signal transduction pathways in cells.

Abstract: The present invention concerns three ubiquitin-conjugating enzymes.

Abstract: The present invention provides a systematic and practical approach for the identification of candidate agents able to inhibit ubiquitin-mediated degradation of a cell-cycle regulatory protein, such as cyclins. One aspect of the present invention relates to a method for identifying an inhibitor of ubiquitin-mediated proteolysis of a cell-cycle regulatory protein by (i) providing a ubiquitin-conjugating system that includes the regulatory protein and ubiquitin under conditions which promote the ubiquitination of the target protein, and (ii) measuring the level of ubiquitination of the subject protein brought about by the system in the presence and absence of a candidate agent. A decrease in the level of ubiquitin conjugation is indicative of an inhibitory activity for the candidate agent.

Abstract: A method of identifying compounds or molecules which alter (enhance or inhibit) stimulation of kinase activity of pre-MPF and, thus, alter (enhance or inhibit) activation of MPF and entry into mitosis. The present method thus makes it possible to identify compounds or molecules which can be administered to regulate the cell cycle; such compounds are also the subject of this invention.

Abstract: The present invention relates to the discovery of novel proteins of mammalian origin which can associate with the human cyclin dependent kinase 4 (CDK4).

Abstract: The subject invention provides an isolated protein having an apparent molecular weight of about 27 kD and capable of binding to and inhibiting the activation of a cyclin E-Cdk2 complex. The subject invention further provides a recombinant nucleic acid molecule which encodes the p27 protein of the subject invention, and related vectors and host vector systems. The subject invention further provides a method for producing the p27 protein of the subject invention using the host vector system. The subject invention further provides methods of determining whether an agent is capable of specifically inhibiting or enhancing the ability of p27 protein to inhibit the activation of cyclin E-Cdk2 complex. Finally, this subject invention provides different uses of the isolated protein, the recombinant nucleic acid molecule encoding the isolated protein and the agent capable of inhibiting or enchancing the ability of p27 protein to inhibit the activation of cyclin E-Cdk2 complex.