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RESEARCH PAPER
Departments of 1 Neuroscience, 2 Medicine, 3 Urology, and 4 Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
Overexpression of the short isoform of p53 (p44) has unexpectedly uncovered a role for p53 in the regulation of size and life span in the mouse. Hyperactivation of the insulin-like growth factor (IGF) signaling axis by p44 sets in motion a kinase cascade that clamps potentially unimpeded growth through p21Cip1. This suggests that pathways of gene activity known to regulate longevity in lower organisms are linked in mammals via p53 to mechanisms for controlling cell proliferation. Thus, appropriate expression of the short and long p53 isoforms might maintain a balance between tumor suppression and tissue regeneration, a major requisite for long mammalian life span.
[Keywords: daf2; GH; growth retardation; aging; testis; Akt; Sir2]
Received October 17, 2003; revised version accepted December 19, 2003.
5 Corresponding author.
E-MAIL hs2n{at}virginia.edu.; FAX (434) 982-4380.
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