Abstract: The present invention relates to a novel assay or screen for identifying compounds with potential therapeutic value for the treatment of protein trafficking diseases such as Cystic Fibrosis (CF) and nephrogenic diabetes insipidus (NDI). The usual approach involves expressing the mutant form of the gene in cells and assaying function in a multiwell format when cells are exposed to libraries of compounds. Although such functional assays are useful, they do not directly test the ability of a compound to correct defective trafficking of the protein. To address this a novel corrector screening assay for CF has been developed in which the appearance of the mutant protein at the cell surface is measured as the assay output. This assay was used to screen more than 3100 compounds. This novel screening approach to protein trafficking diseases is robust and general, and may enable the selection of molecules that can be translated rapidly to a clinical setting.

Abstract: This invention provides compounds of Formula I. The compounds are correctors of ?F508 CFTR trafficking. Also provided are uses of compounds of Formula I for treatment, as well as methods of treatment, of cystic fibrosis.

Abstract: The present invention relates to Candida albicans proteins, such as CaCla4p, Cst20p, CaCdc42p and CaBem1p, associated with virulence and hyphal formation and uses thereof, such as to design screening tests for inhibitors for the treatment of pathogenic fungi infections and/or inflammation conditions. The invention also relates to an in vitro screening test for compounds to inhibit the biological activity of at least one protein selected from the group consisting of CaCla4p, Cst20p, CaCdc42p and CaBem1p, which comprises: a) at least one of said proteins; and b) means to monitor the biological activity of said at least one protein; thereby compounds are tested for their inhibiting potential.

Abstract: The present invention relates to methods of treating and diagnosing protein trafficking disorders and controlling secretory protein production. The present invention also relates to methods for folding unfolded proteins, especially in heterelogous expression systems. The methods comprise exposing an unfolded protein to a biological preparation comprising ERp57 in combination with calnexin or calreticulin under conditions to permit folding of the unfolded protein.

Abstract: The present invention relates to a new yeast two-hybrid system for the detection of interactions between membrane proteins and lumenal proteins of the endoplasmic reticulum. The yeast two-hybrid system of the present invention uses the IRE1 gene of yeast which is a key element in the endoplasmic reticulum unfolded protein response to signal the interaction between proteins within the endoplasmic reticulum. The IRE1 gene codes for a type 1 membrane protein Ire1p, that has a kinase in the cytosolic domain and it signals the presence of unfolded proteins in the ER by oligomerization and transphosphorylation, this in turn activates a RNaseL that has as its unique (so far) substrate the HAC1 messenger RNA, that codes for the transcription factor that binds to the unfolded protein response element and upregulates transcription of ER protein required for folding proteins within the ER.

Abstract: The present invention relates generally to signal transduction through G-protein-coupled receptors and more particularly to the interaction between the &bgr; subunit of the heterotrimeric G-protein and the Ste20p/PAK family of protein kinases. More particularly, the invention is directed to the identification of the G-protein &bgr; subunit interaction domain of Ste20p/PAK family of protein kinases, the Ste20p/PAK interaction domain of G-protein &bgr; subunit, to antibodies specific for these interacting domains, the nucleic acid molecules encoding same, to assays, expression vectors, indicator cells, strains, methods and agents which make use of this Ste20p/PAK—G&bgr; interaction.

Abstract: The present invention relates to a method for determining the effect of a test sample on UGGT activity. The method comprises the steps of: a) exposing an acceptor substrate of UGGT such as acid phosphatase to a labeled donor such as UDP-3H-glucose in the presence of the test sample and UGGT; and b) detecting the amount of donor which was transferred to the acceptor substrate wherein a decrease of donor intake when compared to a control means that the test sample is a UGGT stimulator and a decrease means that the test sample is a UGGT inhibitor. The present invention also relates to an isolated mammalian cDNA which encodes for rat UGGT and to methods of producing mammalian UGGT using recombinant vectors.

Abstract: The present invention provides compositions and methods for increasing secretory protein production. In another aspect, the present invention provides compositions for use in methods of treating and diagnosing protein trafficking disorders. These methods generally involve the alteration of calnexin activity to increase protein secretion or retention.

Abstract: This invention is concerned with the specific processing of secreted proteins in genetically modified yeast cells. The yeast KEX1 gene was cloned and the KEX1 product was shown to be a serine protease, evidently a carboxypeptidase B-like protease. A probable site of processing of polypeptides by the KEX1 gene product is at the C-terminus of the .alpha. subunit of the killer toxin, where the mature toxin subunit is followed in the precursor by a pair of basic amino acid residues. Processing likely involves an endoprotease cut following these basic residues, and their subsequent C-terminal trimming by a carboxypeptidase. Consistent with the KEX1 product being this carboxypeptidase is the finding that it is also involved in .alpha.-factor pheromone production. In wildtype yeast, KEX1 is not essential for .alpha.-factor production, as the final hormone repeat in the prepro .alpha.-hormone precursor does not need C-terminal processing to form one copy of the active hormone. However, in a mutant strain where .