C - Chemistry – Metallurgy – 07 – K
Patent
C - Chemistry, Metallurgy
07
K
C07K 14/47 (2006.01) A61K 9/127 (2006.01) A61K 9/50 (2006.01) A61K 9/70 (2006.01) A61K 31/713 (2006.01) A61K 38/17 (2006.01) A61K 45/00 (2006.01) A61K 48/00 (2006.01) A61P 9/00 (2006.01) C12N 9/12 (2006.01) C12N 15/12 (2006.01)
Patent
CA 2714972
p27KIP1 (p27) blocks cell proliferation through inhibition of 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 factors, 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.
La p27KIP1 (p27) bloque la prolifération des cellules en inhibant la kinase 2 (dk2)1 dépendante des cyclines. Malgré sa solide expression dans le cur2,3, nous en connaissons peu sur la fonction et la régulation de p27 dans ces tissus et dautres tissus non prolifératifs, où lon sait que lexpression de sa principale cible, la cycline E-Cdk2, est très faible. Il est démontré que langiotensine II (Ang II), un important facteur de croissance cardiaque, induit la dégradation des protéasomes de p27 par une phosphorylation dépendante de la protéine kinase CK2-alpha-prime (CK2-alpha-prime) et que p27 inverse lhypertrophie cardiaque compensée établie sans exercer deffet délétère sur la fonction cardiaque. Linvention concerne des méthodes et des compositions pour le traitement de linsuffisance cardiaque et de lhypertrophie cardiaque.
Hauck Ludger
von Harsdorf Ruediger
Bereskin & Parr Llp/s.e.n.c.r.l.,s.r.l.
University Health Network
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