MARKs as modifiers of the p53 pathway and methods of use
OwnerLori Friedman, Gregory D. Plowman +5inventors
InventorsLori Friedman, Gregory D. Plowman, Marcia Belvin, Helen Francis-Lang, Danxi Li, Roel P. Funke, Mario N. Lioubin
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Abstract
Human MARK genes are identified as modulators of the p53 pathway, and thus are therapeutic targets for disorders associated with defective p53 function. Methods for identifying modulators of p53, comprising screening for agents that modulate the activity of MARK are provided.
Claims25
A method of identifying a candidate p53 pathway modulating agent, said method comprising the steps of:
- (a) providing an assay system comprising a purified MARK polypeptide or nucleic acid or a functionally active fragment or derivative thereof;
- (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 p53 pathway modulating agent.
A method for modulating a p53 pathway of a cell comprising contacting a cell defective in p53 function with a candidate modulator that specifically binds to a MARK polypeptide comprising an amino acid sequence selected from group consisting of SEQ ID NOs:24, 25, 26, 27, 28, and 29, whereby p53 function is restored.
A method of modulating p53 pathway in a mammalian cell comprising contacting the cell with an agent that specifically binds a MARK 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 MARK 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.