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AssigneeUniversity Health Network
InventorsRüdiger Von Harsdorf, Ludger Hauck
Estimating the term…
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.
A method of treating a subject having, or at risk of developing, heart failure comprising administering an effective amount of an agent that increases p27 levels.
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A pharmaceutical composition for treating a subject having, or at risk of developing, heart failure, or for inhibiting cardiac myocyte hypertrophy in a cell or subject in need thereof, comprising as active agent an agent that increases p27 levels and a pharmaceutically acceptable carrier, optionally wherein the agent that increases p27 levels comprises a p27 molecule, or an active fragment thereof, optionally wild type p27 or active fragment thereof, or a modified p27 molecule or active fragment thereof, optionally wherein the active fragment comprises or encodes amino acid residues 87-198.
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An isolated polypeptide according to SEQ ID NO:1 wherein amino acid 83 is not serine and/or wherein amino acid 187 is not threonine, optionally wherein amino acid 83 and/or amino acid 187 is aspartic acid.
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Dependencies are inferred from the claim text.