HIF1α delays premature senescence through the activation of MIF

Scott Welford, Barbara Bedogni, Katarina Gradin, Lorenz Poellinger, Marianne Broome Powell, Amato J. Giaccia

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Premature senescence in vitro has been attributed to oxidative stress leading to a DNA damage response. In the absence of oxidative damage that occurs at atmospheric oxygen levels, proliferation of untransformed cells continues for extended periods of time. We have investigated the role of the hypoxia-inducible factor 1α (HIF1α) transcription factor in preventing senescence in aerobic and hypoxic conditions. Using embryonic fibroblasts from a conditional HIF1α knockout mouse, we found that loss of HIF1α under aerobic conditions significantly accelerated the onset of cellular senescence, and decreased proliferation under hypoxia. Furthermore, we identify the macrophage migration inhibitory factor (MIF) as a crucial effector of HIF1α that delays senescence. Inhibition of MIF phenocopies loss of HIF1α. Our findings highlight a novel role for HIF1α under aerobic conditions, and identify MIF as a target responsible for this function.

Original languageEnglish (US)
Pages (from-to)3366-3371
Number of pages6
JournalGenes and Development
Volume20
Issue number24
DOIs
StatePublished - Dec 15 2006
Externally publishedYes

Fingerprint

Hypoxia-Inducible Factor 1
Macrophage Migration-Inhibitory Factors
Cell Aging
Knockout Mice
DNA Damage
Oxidative Stress
Transcription Factors
Fibroblasts
Cell Proliferation
Oxygen

Keywords

  • HIF1α
  • Hypoxia
  • MIF
  • Oxidative stress
  • Senescence

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

HIF1α delays premature senescence through the activation of MIF. / Welford, Scott; Bedogni, Barbara; Gradin, Katarina; Poellinger, Lorenz; Powell, Marianne Broome; Giaccia, Amato J.

In: Genes and Development, Vol. 20, No. 24, 15.12.2006, p. 3366-3371.

Research output: Contribution to journalArticle

Welford, S, Bedogni, B, Gradin, K, Poellinger, L, Powell, MB & Giaccia, AJ 2006, 'HIF1α delays premature senescence through the activation of MIF', Genes and Development, vol. 20, no. 24, pp. 3366-3371. https://doi.org/10.1101/gad.1471106
Welford, Scott ; Bedogni, Barbara ; Gradin, Katarina ; Poellinger, Lorenz ; Powell, Marianne Broome ; Giaccia, Amato J. / HIF1α delays premature senescence through the activation of MIF. In: Genes and Development. 2006 ; Vol. 20, No. 24. pp. 3366-3371.
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