Abstract: Dimerization and oligomerization of proteins are general biological control mechanisms that contribute to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins. In principle, any two target proteins can be induced to associate by treating the cells or organisms that harbor them with cell permeable, synthetic ligands. To illustrate the practice of tis invention, we have induced: (1) the intracellular aggregation of the cytoplasmic tail of the .zeta.

Abstract: Dimerization and oligomerization of proteins are general biological control mechanisms that contribute to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins. In principle, any two target proteins can be induced to associate by treating the cells or organisms that harbor them with cell permeable, synthetic ligands. To illustrate the practice of this invention, we have induced: (1) the intracellular aggregation of the cytoplasmic tail of the .zeta.

Abstract: The present invention derives from the discovery that CDC25 phosphatases and Raf proteins are able to physically interact to form protein-protein complexes, with the Raf protein mediating the activation of CDC25 phosphatases. The present invention provides both cell-free and cellular assays for detecting agents which modulate the ras-dependent activation of CDC25, as for example, by affecting the binding of a CDC25 protein with Raf, or Raf-associated complexes. Also disclosed is a method for transforming/immortalizing cells, particularly primary cell cultures.

Abstract: Methods for isolating patched genes, particularly mammalian patched genes, including mouse and human patched genes, as well as invertebrate patched genes and sequences, are provided. Loss-of function of the patched is associated with the occurrence of human cancers, particularly basal cell carcinomas of the skin. The cancers may be familial, having as a component of risk an inherited genetic predisposition, or may be sporadic. Therefore, methods for using the patched gene as a diagnostic for assessing a genetic predisposition to cancer, and to identify specific cancers having mutations in this gene, are disclosed.

Abstract: The present invention relates to methods and compositions for the elucidation of mammalian gene function. Specifically, the present invention relates to methods and compositions for improved mammalian complementation screening, functional inactivation of specific essential or non-essential mammalian genes, and identification of mammalian genes which are modulated in response to specific stimuli.In particular, the compositions of the present invention include, but are not limited to, replication-deficient retroviral vectors, libraries comprising such vectors, retroviral particles produced by such vectors in conjunction with retroviral packaging cell lines, integrated provirus sequences derived from the retroviral particles of the invention and circularized provirus sequences which have been excised from the integrated provirus sequences of the invention. The compositions of the present invention further include novel retroviral packaging cell lines.

Abstract: The present invention relates to the discovery in mammalian cells, particularly human cells, of a novel CDK-binding protein, referred to herein as "cdc37". As described herein, this protein functions to facilitate activation and accordingly finctions in the modulation of cell-cycle progression, and therefore ultimately of cell growth and differentiation. Moreover, binding data indicated that cdc37 may function coordinately with other cell-cycle regulatory proteins, such as of cyclin-dependent kinases (CDKs), src, p53 and erk kinases.

Abstract: The present invention relates to chimeric transcriptional activators.

Abstract: Dimerization and oligomerization of proteins are general biological control mechanisms that contribute to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins. In principle, any two target proteins can be induced to associate by treating the cells or organisms that harbor them with cell permeable, synthetic ligands. To illustrate the practice of this invention, we have induced: (1) the intracellular aggregation of the cytoplasmic tail of the .zeta.

Abstract: We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins and disclose methods and materials for using that procedure to regulatably initiate cell-specific apoptosis (programmed cell death) in genetically engineered cells.

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: The present invention relates to a process for stereoselective or regioselective chemical synthesis which generally comprises reacting a nucleophile and a chiral or prochiral cyclic substrate in the presence of a non-racemic chiral catalyst to produce a stereoisomerically or regioselectively enriched product.

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

Abstract: A programmable pacing device for helping a user to achieve a desired pace or tempo. The device is capable of emitting a plurality of different audible signals, each signal conveying selected pacing information to the user, and may be used by athletes to help in training or race pacing. The device may comprise a single unit or two separate units; an input unit and a signaling unit and as a single unit the device may form part of a pair of swimming goggles.

Abstract: The subject invention features substituted N-heteroaromatic compounds, libraries of substituted N-heteroaromatic compounds, and methods of synthesis thereof. For example, the present invention provides methods for synthesizing substituted N-heteroaromatic compounds, and is particularly amenable to the generation of libraries of substituted N- heteroaromatic compounds by combinatorial chemistry. The methods of the invention generally feature the reaction of O-linked heteroaromatic N-oxides with nucleophiles to produce substituted N-heteroaromatic compounds.

Abstract: Methods and compositions are provided for modified cells, where a chimeric protein consisting of a ligand binding domain fused to an action domain is employed which initiates a signal which activates a biological process: transcription of at least one gene, usually a second construct introduced into the host cells; exocytosis; or an extracellular process. The second construct optimally present provides for a promoter which responds to a transcriptional activation action domain to provide for transcription, when an appropriate ligand binds to the ligand binding domain. Exemplary of the system is the use of an FKBP/CD3.zeta. or transcription factor fusion protein, using dimeric FK506 or FK520 as the ligand and a promoter responsive to NF-AT or other transcription factor requiring two molecules for transcriptional activation.

Abstract: Dimerization and oligomerization of proteins are general biological control mechanisms that contribute to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins. In principle, any two target proteins can be induced to associate by treating the cells or organisms that harbor them with cell permeable, synthetic ligands. To illustrate the practice of this invention, we have induced: (1) the intracellular aggregation of the cytoplasmic tail of the .zeta.

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 makes available assays and reagents for identifying agents which can be used to modulate at least one proliferation, differentiation and cell death by apoptosis.

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.