TAOJIKs as modifiers of the beta-catenin pathway and methods of use
AssigneeExelixis, Inc.
InventorsMichael A. Costa, Steven Brian Gendreau, Emery G. Dora III, Monique Nicoll, Lenore Urbani, Jeffrey S. Larson
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Abstract
Human TAOJIK genes are identified as modulators of the beta-catenin pathway, and thus are therapeutic targets for disorders associated with defective beta-catenin function. Methods for identifying modulators of beta-catenin, comprising screening for agents that modulate the activity of TAOJIK are provided.
Claims26
A method of identifying a candidate beta-catenin pathway modulating agent, said method comprising the steps of:
- (a) providing an assay system comprising a TAOJIK polypeptide or nucleic acid;
- (b) contacting the assay system with a test agent under conditions whereby, but for the presence of the test agent, the system provides a reference activity;
- and
- (c) detecting a test agent-biased activity of the assay system, wherein a difference between the test agent-biased activity and the reference activity identifies the test agent as a candidate beta-catenin pathway modulating agent.
The method of claim II wherein the model system is a mouse model with defective beta-catenin function.
A method for modulating a beta-catenin pathway of a cell comprising contacting a cell defective in beta-catenin function with a candidate modulator that specifically binds to a TAOJIK polypeptide comprising an amino acid sequence selected from group consisting of SEQ ID NOs:16, 17, and 18 whereby beta-catenin function is restored.
A method of modulating beta-catenin pathway in a mammalian cell comprising contacting the cell with an agent that specifically binds a TAOJIK polypeptide or nucleic acid.
A method for diagnosing a disease in a patient comprising:
- (a) obtaining a biological sample from the patient;
- (b) contacting the sample with a probe for TAOJIK expression;
- (c) comparing results from step (b) with a control;
- (d) determining whether step (c) indicates a likelihood of disease.
Dependencies are inferred from the claim text.