Nature article

Lou Pagnucco pagnucco at oeonline.com
Sat Nov 20 00:07:37 EST 1999


Very exciting.

It would be interesting to know if:

(1) concentration if proteins regulated by the p66shc gene are species
      dependent and, if so, whether whether such proteins are more
abundantly
      produced in species with shorter life spans.

(2)  the cells of these genetically modified mice have an extended
      "Hayflick" limit.

(3) the antioxidant PBN (and its chemical relatives) which are reputed to
      reduce the concentration of oxidized proteins reduce the level of
      p66shc proteins.


Magnus Lynch wrote in message <3833ED6B.9292618D at cam.ac.uk>...
>This article was published in this November's edition of Nature. It
>looks extremely interesting:
>
>The p66shc adaptor protein controls oxidative stress response and life
>span in mammals
>
>ENRICA MIGLIACCIO, MARCO GIORGIO, SIMONETTA MELE, GIULIANA PELICCI,
>PAOLO REBOLDI,
>PIER PAOLO PANDOLFI, LUISA LANFRANCONE & PIER GIUSEPPE PELICCI
>
>Gene mutations in invertebrates have been identified that extend life
>span and enhance resistance to environmental stresses
>such as ultraviolet light or reactive oxygen species. In mammals, the
>mechanisms that regulate stress response are poorly
>understood and no genes are known to increase individual life span. Here
>we report that targeted mutation of the mouse
>p66shc gene induces stress resistance and prolongs life span. p66shc is
>a splice variant of p52shc/p46shc (ref. 2), a
>cytoplasmic signal transducer involved in the transmission of mitogenic
>signals from activated receptors to Ras. We show
>that: (1) p66shc is serine phosphorylated upon treatment with hydrogen
>peroxide (H2O2) or irradiation with ultraviolet light;
>(2) ablation of p66shc enhances cellular resistance to apoptosis induced
>by H2O2 or ultraviolet light; (3) a
>serine-phosphorylation defective mutant of p66shc cannot restore the
>normal stress response in p66shc-/- cells; (4) the p53
>and p21 stress response is impaired in p66shc-/- cells; (5) p66shc-/-
>mice have increased resistance to paraquat and a 30%
>increase in life span. We propose that p66shc is part of a signal
>transduction pathway that regulates stress apoptotic
>responses and life span in mammals.
>
>Magnus Lynch







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