Modulation of mammalian life span by the short isoform of p53

Bernhard Maier, Wendy Gluba, Brian Bernier, Terry Turner, Khalid Mohammad, Theresa Guise, Ann Sutherland, Michael Thorner, Heidi Scrable

Research output: Contribution to journalArticle

455 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)306-319
Number of pages14
JournalGenes and Development
Volume18
Issue number3
DOIs
StatePublished - Feb 1 2004

Keywords

  • Aging
  • Akt
  • Daf2
  • GH
  • Growth retardation
  • Sir2
  • Testis

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Maier, B., Gluba, W., Bernier, B., Turner, T., Mohammad, K., Guise, T., Sutherland, A., Thorner, M., & Scrable, H. (2004). Modulation of mammalian life span by the short isoform of p53. Genes and Development, 18(3), 306-319. https://doi.org/10.1101/gad.1162404