THE cAMP/PKA/HDAC5 PATHWAY AND USES THEREOF

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-12. (canceled)

A method of preventing cardiac myopathy or of preventing or delaying the occurrence of heart failure in a subject, comprising administering to the subject an agent that increases cAMP/PKA/HDAC5 pathway activity.

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-22. (canceled)

A method of treating heart failure comprising administering to the subject an agent that decreases cAMP/PKA/HDACS pathway activity.

-27. (canceled)

A method of treating heart failure in a subject comprising administering to the subject an agent that inhibits HDAC5-mediated transcriptional repression of MEF2.

-33. (canceled)

A method of identifying a compound that inhibits cardiac myopathy via the cAMP/PKA/HDAC5 pathway comprising:

• a) contacting a cardiomyocyte with a test compound, wherein the cardiac myocyte is subjected to stress;
• and
• b) measuring phosphorylation of HDAC5 at Ser280, wherein an increase in phosphorylation indicates that the test compound inhibits cardiac myopathy via the cAMP/PKA/HDAC5 pathway.

(canceled)

A method of identifying a compound that inhibits cardiac myopathy via the cAMP/PKA/HDAC5 pathway comprising:

• a) contacting a cardiomyocyte with a test compound, wherein the cardiac myocyte is subjected to stress;
• and
• b) measuring the association of HDAC5 with 14-3-3 protein, a decrease in the association between HDAC5 and 14-3-3 indicating that the test compound inhibits cardiac myopathy via the cAMP/PKA/HDAC5 pathway.

(canceled)

A method of identifying a compound that inhibits the binding of HDAC5 to PKA comprising:

• a) contacting HDAC5 with a test compound in the presence of PKA;
• and
• b) detecting binding of HDAC5 to PKA, a decrease in binding compared to a control indicating that the test compound inhibits binding of HDAC5 to PKA.

A method of identifying a compound that inhibits binding of HDAC5 to PKA comprising:

• a) contacting a cell that comprises HDAC5, PKA and a construct containing an MEF2 regulatory region operatively linked to a nucleic acid encoding luciferase with a test compound;
• and
• b) detecting the level of luciferase activity, an increase in luciferase activity indicating that the compound inhibits binding of HDAC5 to PKA.

A method of identifying a compound that inhibits HDAC5-mediated transcriptional repression of MEF2 comprising:

• a) contacting a cell with a test compound;
• and
• b) detecting the level of expression of MEF2-dependent gene(s), wherein an increase in expression of MEF2 dependent genes as comparted to control indicates that the test compound is a compound that inhibits HDAC5-mediated transcriptional repression of MEF2.