Abstract: The present invention provides novel therapeutic molecules called Culling Fusion Proteins (CFPs) that allow the continuous removal of therapeutic targets from extracellular space by exploiting the endosome/lysosome intracellular degradation pathway, and the exocytotic pathway in a combined manner. The products of the invention, by appropriately utilizing the cellular endocytosis and exocytosis mechanism, can be recycled multiple times by cells to eliminate undesired molecules, therefore such therapeutic molecules can be administered at low concentration.

Abstract: Disclosed are complexes of the NlK1 protein and proteins identified as interacting with the NlK1 protein (NlK1 protein-IPs). The NlK-1 interacting proteins include TrkA, protein phosphatase 1&agr;, 14-3-3&egr;, &agr;-tropomyosin, vimentin, p0071, Ini-1, and newly described proteins named IP-1, IP-2, IP-3, IP-4, and IP-5. Also described are derivatives, fragments analogs and homologs of these proteins. Methods of screening these complexes for efficacy in treating and/or preventing various diseases and disorders, particularly, neoplasia, neurodegenerative disease, hypertrophic cardiomyopathy, viral infections and metabolic diseases and disorders are also disclosed.

Abstract: The present invention discloses complexes of the Nlk1 protein with proteins identified as interacting with the Nlk1 protein (Nlk1 protein-IPs) by a modified, improved yeast two hybrid assay system. The proteins which were identified to interact with the Nlk1 protein, and thus form complexes, included: TrkA, protein phosphatase 1&agr;, 14-3-3&egr;, &agr;-tropomyosin, vimentin, p0071, Ini-1, IP-1, IP-2, IP-3, IP-4 and IP-5, as well as derivatives, fragments analogs and homologs thereof. Methodologies of screening these aforementioned complexes for efficacy in treating and/or preventing various diseases and disorders, particularly, neoplasia, neurodegenerative disease, hypertrophic cardiomyopathy, viral infections and metabolic diseases and disorders are also disclosed herein.