Abstract: p27KIP1 (p27) blocks cell proliferation through inhibition of FIG. 6 cyclin-dependent kinase 2 (dk2)1. Despite its robust expression in the heart2,3, little is known about both the function and regulation of p27 in this and other non-proliferative tissues, where the expression of its main target, cyclin E-Cdk2 is known to be very low4. Angiotensin II (Ang II), a major cardiac growth factor5, is demonstrated to induce the proteasomal degradation of p27 through protein kinase CK2-alpha-prime (CK2-alpha-prime) dependent phosphorylation and p27 is demonstrated to reverse established compensated cardiac hypertrophy without exerting any deleterious effect on cardiac function. Provided are methods and compositions for treating heart failure and cardiac hypertrophy.