Induction of apoptosis by cellular stress
AssigneesDana-Farber Cancer Institute, Inc., The University of Chicago
InventorsDonald W. Kufe, Rima Kaddurah-Daouk, Ralph R. Weichselbaum
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Abstract
The invention provides methods of screening to identify compounds that modulate the ability of a protein to translocate to the mitochondria when a cell is subjected to cellular stress. Such compounds can be useful to modulate the level of apoptosis in a cell. For example, compounds identified according to the methods described herein can be used to treat disorders characterized by excessive apoptosis, e.g., a neurological disorder, or insufficient apoptosis, e.g., cancer.
Claims19
A method of identifying a compound that inhibits mitochondrial translocation of a protein kinase, the method comprising:
- providing a cell;
- subjecting the cell to a cellular stress, wherein the cellular stress induces mitochondrial translocation of the protein kinase;
- contacting the cell with a test compound;
- and
- determining whether mitochondrial translocation of the protein kinase is decreased when the cell is contacted with the test compound,
- the decrease being an indication that the test compound inhibits mitochondrial translocation of the protein kinase.
The method of claim wherein the cell is subjected to oxidative stress by contacting the cell with hydrogen peroxide (H2O2).
A method of identifying a compound that increases mitochondrial translocation of a protein kinase, the method comprising:
- providing a cell;
- contacting the cell with a test compound;
- and
- determining whether mitochondrial translocation of the protein kinase is increased when the cell is contacted with the test compound,
- the increase being an indication that the test compound increases mitochondrial translocation of the protein kinase.
A method of identifying a protein that is translocated to the mitochondria upon the induction of oxidative stress, the method comprising:
- providing a cell;
- subjecting the cell to a oxidative stress;
- and
- identifying a protein that is translocated to the mitochondria of the cell.
Dependencies are inferred from the claim text.