Nature article

Magnus Lynch mdl24 at cam.ac.uk
Thu Nov 18 07:13:31 EST 1999


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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