Abstract:
The present invention relates to the discovery of protein-protein interactions that are involved in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD). Thus, the present invention is directed to complexes of these proteins and/or their fragments, antibodies to the complexes, diagnosis of neurodegenerative disorders (including diagnosis of a predisposition to and diagnosis of the existence of the disorder), drug screening for agents which modulate the interaction of proteins described herein, and identification of additional proteins in the pathway common to the proteins described herein.
Abstract:
By analyzing the mechanism for inducing a histone deacetylase inhibitor (Trichostatin A)-mediated expression of cyclin-CDK inhibitory factor having a proliferation suppressing effect (tumor-suppressing effect), it was revealed that the binding of Sp3 to the Sp1 binding sequence within a promoter is important in the expression of the above factor. Thus, a novel antitumor agent can be developed by screening a pharmaceutical agent capable of elevating Sp3 activity.
Abstract:
The present invention provides improved reverse hybrid assay methods for identifying amino acid residues within a protein that are required for its interaction or physical association with another protein, wherein disruption of an interaction between a protein of interest and its binding partner protein is assayed for a library of mutations of said protein of interest, and maintenance of an interaction between the protein of interest and another binding partner is assayed simultaneously in a single step, thereby reducing the incidence of uninformative mutations in the protein of interest that are detected.
Abstract:
The present invention provides compounds and methods for the detection of protein-protein interactions wherein said interactions are dependent on the presence or absence of post-translational modifications (PTMs) of at least one of the proteins.
Abstract:
Methods, assays, and components are described in which biological samples can be rapidly and sensitively analyzed for the presence of species associated with neurodegenerative disease. Techniques and components are provided for diagnosis of disease, as well as for screening of candidate drugs for treatment of neurodegenerative disease. The techniques are simple, extremely sensitive, and utilize readily-available components. Binding species, capable of binding a neurodegenerative disease aggregate-forming or aggregate-forming species, are fastened to surfaces of electrodes and surfaces of particles, or provided free in solution, to bind aggregate-forming species and/or be involved in aggregation.
Abstract:
Disclosed herein are methods for detecting complex protein interactions and protein functional relationships, and reagents for carrying out those methods.
Abstract:
This invention provides methods of determining whether a compound inhibits HIV-1 reverse transcriptase. This invention provides methods of determining whether a compound inhibits formation of a complex between a p66 and p51 subunit polypeptides of HIV-1 reverse transcriptase. This invention provides a method of determining whether a compound enhances formation of a complex between a p66 and p51 subunit polypeptides of HIV-1 reverse transcriptase. This invention provides methods of determining whether a compound inhibits formation of a complex between two p66 subunit polypeptides of HIV-1 reverse transcriptase. This invention provides methods of determining whether a compound enhances formation of a complex between two p66 subunit polypeptides of HIV-1 reverse transcriptase.
Abstract:
A method of identifying proteins able to interact via protein-protein interactions with a protein of interest, comprising (a) performing a first assay to identify cells expressing a reporter gene, wherein the first assay is transcription-based two-hybrid screening system; (b) obtaining DNA from the cells identified in step (a) via a PCR procedure; and (c) performing a second assay on the DNA obtained in step (b), wherein the second assay is a non-transcription-based two-hybrid screening system, to identify cells expressing a reporter gene, wherein positive cells identified in step (a) that are found to be positive in step (c) express a protein able to interact via protein-protein interactions with a protein of interest.
Abstract:
The present invention relates provides an improved reverse n-hybrid screening method for identifying antagonists or inhibitors of biological interactions, wherein multiple reporter genes are employed to distinguish antagonists or inhibitors of one interaction from those antagonists or inhibitors of other interactions, particularly where each of said interactions involves one or more common interacting partners. A further aspect of the invention provides novel expression vectors for performing the inventive method, particularly in high throughput screens.
Abstract:
Disclosed are methods for identifying molecular interactions (e.g., protein/protein, protein/DNA, protein/RNA, or RNA/RNA interactions). All of the methods within the invention employ counterselection and at least two hybrid molecules. Molecules which interact reconstitute a transcription factor and direct expression of a reporter gene, the expression of which is then assayed. Also disclosed are genetic constructs which are useful in practicing the methods of the invention.