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AssigneeExelixis, Inc.
InventorsMario N. Lioubin, Lori Friedman, Marcia Belvin, Jeffrey S. Larson, Changyou Chen, Stephanie A. Robertson, Wen Shi, Jocelyn Chan, Danxi Li, Helen Francis-Lang, Gregory D. Plowman, Roel P. Funke, Michael Schoor, Branko Zevnik, Gunther Kauselmann, Hartmut Tintrup
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RRP genes are identified as modulators of the p53 or p21 pathway, and thus are therapeutic targets for disorders associated with defective p53 or p21 function. Methods for identifying modulators of p53 or p21, comprising screening for agents that modulate the activity of RRP are provided. Modulating agents identified using the methods of the invention can be used to specifically inhibit growth of tumor cells that overexpress an RRP protein. mRRP1 knockout mice are also provided.
A method of specifically inhibiting growth of tumor cells that overexpress an RRP protein comprising contacting said tumor cells with an amount of an exogenous RRP binding agent that results in inhibition in growth of tumor cells.
A method of screening for agents that modulate the interaction of an RRP polypeptide with an RRP binding target, comprising:
A method of diagnosing a tumor cell as having abnormal p53 or p21 pathway signaling, comprising measuring RRP expression levels in said tumor cell, wherein increased RRP expression levels in the tumor cell compared to a non-tumor cell of the same tissue or organ as the tumor cell, indicates defective p53 or p21 pathway signaling in the tumor cell.
A method of identifying a candidate p53 or p21 pathway modulating agent, said method comprising the steps of:
A method for modulating a p53 or p21 pathway of a cell comprising contacting a cell defective in p53 or p21 function with a candidate modulator that specifically binds to an RRP polypeptide comprising an amino acid sequence selected from group consisting of SEQ ID NOs:2, 4, 6, 8, 10, 12, 14, 16, and 46 whereby p53 or p21 function is restored.
A method of modulating p53 or p21 pathway in a mammalian cell comprising contacting the cell with an agent that specifically binds a RRP polypeptide or nucleic acid.
A method for diagnosing a disease in a patient comprising:
A purified nucleic acid molecule that encodes a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:46, or reverse complement thereof.
A recombinant expression system comprising a DNA or RNA molecule, wherein said expression system is capable of producing an MRRP1 polypeptide comprising the amino acid sequence of SEQ ID NO:46 when said expression system is present in a compatible host cell.
A recombinant host cell expressing the protein produced by the method of claim.
A transgenic mouse whose genome comprises a disruption in an endogenous RRP gene wherein said disruption results in decreased expression or a lack of expression of said endogenous RRP gene.
A mouse cell whose genome comprises a disruption in an endogenous RRP gene wherein said disruption results in decreased expression or a lack of expression of said endogenous RRP gene.
A method of selecting an agent that modulates cell proliferation comprising:
Dependencies are inferred from the claim text.