HIF1alpha Delays Premature Senescence Through the Activation of MIF

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2006 Dec 5

PMID 17142669

Citations 87

Authors

Scott M Welford

Barbara Bedogni

Katarina Gradin

Lorenz Poellinger

Marianne Broome Powell

Amato J Giaccia

Affiliations

Soon will be listed here.

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 1alpha (HIF1alpha) transcription factor in preventing senescence in aerobic and hypoxic conditions. Using embryonic fibroblasts from a conditional HIF1alpha knockout mouse, we found that loss of HIF1alpha 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 HIF1alpha that delays senescence. Inhibition of MIF phenocopies loss of HIF1alpha. Our findings highlight a novel role for HIF1alpha under aerobic conditions, and identify MIF as a target responsible for this function.

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