Methods to identify compounds useful for tumor sensitization to dna damage
AssigneeNew York University
InventorsMichele Pagano, Luca Busino
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AssigneeNew York University
InventorsMichele Pagano, Luca Busino
Estimating the term…
Cdc25A is herein identified as a substrate for β-TrCP1- or β-TrCP2-mediated ubiquitination and subsequent degradation via the ubiquitin-proteasome pathway. In particular, it has been found that interfering with β-TrCP expression or function, or increasing β-TrCP degradation, leads to accumulation of Cdc25A in a cell. Since degradation of Cdc25A is a key feature of the response to DNA damage, leading to a stall in the cell cycle during which the cell can repair the damage, Cdc25A accumulation can abolish this response, thereby sensitizing the cell to DNA damage. Described herein are assays for identifying β-TrCP inhibitors, and method of using such inhibitors for modulating Cdc25A degradation, sensitization of tumor cells, and as adjuvants in cancer therapy based on DNA damaging agents.
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A method of screening for an agent useful for sensitizing a cancer cell to DNA damage by a second agent which comprises:
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A method of screening for an agent useful for sensitizing a cancer cell to DNA damage by a second agent which comprises:
A method of screening for an agent useful in sensitizing a cancer cell to DNA damage by a second agent which comprises:
A kit for screening for an agent useful for sensitizing a cancer cell to DNA damage by a second agent, which comprises a β-TrCP, Cdc25A protein, means β for detecting binding between the β-TrCP and the Cdc25A protein, and instructions for use.
A kit for screening for an agent useful for reducing Cdc25A degradation, which comprises a β-TrCP, Cdc25A protein, means for detecting binding between the β-TrCP and the Cdc25A protein, and instructions for use.
Dependencies are inferred from the claim text.