Reagents and methods for identifying and modulating expression of genes regulated by CDK inhibitors
OwnerIgor B. Roninson, Jason C. Pooleinventors
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Abstract
This invention provides methods and reagents for identifying compounds that inhibit the induction of genes involved in viral infection, cancer and age-related diseases, such genes being induced by cyclin-dependent kinase inhibitors.
Claims104
A recombinant expression construct encoding a reporter gene operably linked to a promoter from a mammalian viral or cellular gene induced by a cyclin-dependent kinase inhibitor.
A method for identifying a compound that inhibits CDK inhibitor-mediated induction of viral or cellular gene expression, the method comprising the steps of:
- (a) producing expression of a CDK inhibitor in a mammalian cell;
- (b) assaying the cell in the presence of the compound for changes in expression of cellular genes whose expression is modulated by the CDK inhibitor;
- and
- (c) identifying the compound as an inhibitor of CDK inhibitor-mediated modulation of viral or cellular gene expression if expression of the cellular genes of subpart (b) is changed to a lesser extent in the presence of the compound.
A method for identifying a compound that inhibits CDK inhibitor-mediated induction of viral or cellular gene expression in a mammalian cell, the method comprising the steps of:
- (a) treating the mammalian cell in the presence and absence of the compound with an agent or culturing the mammalian cell under conditions that induce senescence;
- (b) assaying the mammalian cell for induction of viral or cellular genes that are induced by CDK inhibitor gene expression;
- and
- (c) identifying the compound as an inhibitor of CDK inhibitor-mediated induction of viral or cellular gene expression if genes that are induced by the CDK inhibitor are induced to a lesser extent, in the presence of the compound than in the absence of the compound.
A method for identifying a compound that inhibits CDK inhibitor-mediated induction of viral or cellular gene expression in a mammalian cell, the method comprising the steps of:
- (a) contacting a mammalian cell in the presence or absence of the compound with an agent or culturing the mammalian cell under conditions that induce senescence, wherein the cell comprises a reporter gene under the transcriptional control of a promoter for a mammalian viral or cellular gene whose expression is modulated by a CDK inhibitor;
- (b) assaying the cell for changes in expression of the reporter gene;
- and
- (c) identifying the compound as an inhibitor of CDK inhibitor-mediated induction of viral or cellular gene expression if expression of the reporter gene is changed to a lesser degree in the presence of the compound than in the absence of the compound.
A method for inhibiting CDK inhibitor-mediated induction of viral or cellular gene expression, the method comprising the step of contacting the cell with an effective amount of a compound that inhibits NFκB activity.
A method for treating a disease in an animal accompanied by CDK inhibitor induced gene expression, the method comprising the step of administering to the animal an effective amount of a non-steroidal anti-inflammatory drug (NSAID) that inhibits NFκB activity.
A compound that inhibits viral or cellular genes associated with pathogenic consequences of senescence in a mammalian cell, wherein the compound is produced by a method having the steps of:
- (a) treating the mammalian cell in the presence of the compound with an agent or culturing the mammalian cell under conditions that induce senescence;
- (b) assaying the mammalian cell for induction of cellular genes that are induced by CDK inhibitor gene expression;
- and
- (c) identifying the compound as an inhibitor of senescence if genes that are induced by the CDK inhibitor are induced to a lesser extent, in the presence of the compound.
A compound that inhibits production of viral or cellular gene products induced by a CDK inhibitor in a mammalian cell, wherein the compound is produced by a method having the steps of:
- (a) treating the mammalian cell in the presence of the compound with an agent or culturing the mammalian cell under conditions that induce expression of a CDK inhibitor;
- (b) assaying the mammalian cell for induction of viral or cellular genes that are induced by CDK inhibitor gene expression;
- and
- (c) identifying the compound as an inhibitor of CDK inhibitor induction if genes that are induced by the CDK inhibitor are induced to a lesser extent, in the presence of the compound.
A method for inhibiting production of anti-apoptotic or mitogenic factors in a mammalian cell, the method comprising the steps of contacting the cell with a compound that inhibits induction of gene expression by a CDK inhibitor.
A method for selectively inhibiting induction of genes induced by a CDK inhibitor in an animal, comprising administering an NFκB inhibitor to an animal in need of such treatment.
Dependencies are inferred from the claim text.