Nuclear accumulation of glycogen synthase kinase-3 during replicative senescence of human fibroblasts

Jaroslaw W. Zmijewski, Richard S Jope

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Activation of the tumor suppressor protein p53 contributes to cellular senescence. As glycogen synthase kinase-03 (GSK3) was recently found to interact with p53 and contribute to the actions of p53, this study examined whether GSK3 accumulated in the nucleus and associated with p53 in senescent cells. Compared with young and middle-aged human WI-38 fibroblasts, senescent cells were found to contain increased nuclear levels of GSK3β, and also tended to accumulate in the nucleus the other isoform of GSK3, GSK3α. Co-immunoprecipitation experiments demonstrated that GSK3β and p53 formed a complex in the nucleus. Further experiments tested whether inhibition of GSK3 altered the development of senescence using long-term treatment with the selective GSK3 inhibitor lithium. Lithium treatment reduced the senescence-associated accumulation of p53 and caused cells to enter a reversible quiescent state. These results indicate that a portion of the p53 that is activated in senescent cells is modulated by its association with GSK3β in the nucleus, an association that is known to facilitate the actions of p53 and that may contribute to senescence.

Original languageEnglish
Pages (from-to)309-317
Number of pages9
JournalAging Cell
Volume3
Issue number5
DOIs
StatePublished - Oct 1 2004
Externally publishedYes

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Glycogen Synthase Kinase 3
Glycogen Synthase Kinases
Cell Aging
Fibroblasts
Lithium
Tumor Suppressor Protein p53
Immunoprecipitation
Protein Isoforms

Keywords

  • GSK3
  • Lifespan
  • Lithium
  • p21
  • p53
  • Senescence

ASJC Scopus subject areas

  • Cell Biology

Cite this

Nuclear accumulation of glycogen synthase kinase-3 during replicative senescence of human fibroblasts. / Zmijewski, Jaroslaw W.; Jope, Richard S.

In: Aging Cell, Vol. 3, No. 5, 01.10.2004, p. 309-317.

Research output: Contribution to journalArticle

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