Materials and methods relating to modulation of p66 expression

Details Materials and methods relating to modulation of p66 expression Materials and methods relating to modulation of p66 expression

C - Chemistry, Metallurgy

12

N

C12N 15/12 (2006.01) A61K 31/70 (2006.01) A61K 39/395 (2006.01) C07K 14/47 (2006.01) C12N 15/11 (2006.01) C12Q 1/68 (2006.01) G01N 33/53 (2006.01)

Patent

CA 2367464

It has been determined that i) p66shc is serine phosphorylated upon UV treatment or oxidative damage; ii) the serine-phosphorylation of p66 by oxidative signals is mediated by Erk1 and p38, as shown both in vivo and in vitro; iii) ablation of p66shc expression by homologous recombination enhances resistance to oxidative damage both in vitro and in vivo; iv) a serine- phosphorylation defective mutant of p66shc is unable to restore a normal stress response in p66shc targeted cells; v) mice carrying the p66shc targeted mutation have prolonged lifespan.

On a déterminé que i) le gène p66?shc¿ est phosphorylé au niveau de la sérine par traitement aux ultraviolets ou par lésion oxidative; ii) la phosphorylation au niveau de la sérine du gène p66 au moyen de signaux oxidatifs est véhiculée par Erk1 et p38, à la fois in vivo et in vitro; iii) une ablation de l'expression du p66?shc¿ par recombinaison homologue augmente la résistance aux lésions oxidatives in vitro et in vivo; iv) un mutant de p66?shc¿ qui est privé de la phosphorylation au niveau de sa sérine est incapable de rétablir une réponse normale au stress dans les cellules ciblées du p66?shc¿; v) des souris porteuses de la mutation ciblée de p66?shc¿ ont une plus grande espérance de vie.

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