Reagents and methods for identifying and modulating expression of genes regulated by p21
OwnerBey-Dih Chang, Igor Roninsoninventors
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Abstract
This invention provides methods and reagents for identifying genes involved in cell cycle progression, growth promotion, modulation of apoptosis, cellular senescence and aging, and methods for identifying compounds that inhibit or potentiate cellular senescence.
Claims25
A method for identifying a compound that inhibits senescence-associated changes in 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 that induces senescence or culturing the mammalian cell under conditions that induce senescence;
- (b) assaying the mammalian cell for repression or induction of a cellular gene that is repressed or induced by p21 gene expression;
- and
- (c) identifying the compound as an inhibitor of senescence-associated changes in cellular gene expression if the gene that is repressed by p21 is repressed to lesser extent, or the gene that is induced by p21 is 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 promotes senescence-associated changes in cellular gene expression in a mammalian cell, the method comprising the steps of:
- (d) treating the mammalian cell with an agent that induces senescence or culturing the mammalian cell under conditions that induce senescence in the presence and absence of the compound;
- (e) assaying the mammalian cell for repression or induction of a cellular gene that is repressed or induced by p21 gene expression;
- and
- (f) identifying a compound that promotes senescence-associated changes in cellular gene expression if a gene that is repressed by p21 is repressed in the presence of the compound, or a gene that is induced by p21 is induced in the presence of the compound.
A method for identifying a compound that induces senescence-associated changes in cellular gene expression in a mammalian cell, the method comprising the steps of:
- (a) assaying a mammalian cell in the presence and absence of the compound for expression of a gene whose expression is modulated by p21;
- and
- (b) identifying a compound that induces senescence-associated changes in cellular gene expression if expression of a gene that is repressed by p21 is repressed in the cell, or expression of a gene that is induced by p21 is increased in the cell, to a greater extent in the presence than in the absence of the compound.
Dependencies are inferred from the claim text.