A proinflammatory cytokine inhibits p53 tumor suppressor activity.
p53 has a key role in the negative regulation of cell proliferation, in the maintenance of genomic stability, and in the suppression of transformation and tumorigenesis. To identify novel regulators of p53, we undertook two functional screens to isolate genes which bypassed either p53-mediated growth arrest or apoptosis. In both screens, we isolated cDNAs encoding macrophage migration inhibitory factor (MIF), a cytokine that was shown previously to exert both local and systemic proinflammatory activities. Treatment with MIF overcame p53 activity in three different biological assays, and suppressed its activity as a transcriptional activator. The observation that a proinflammatory cytokine, MIF, is capable of functionally inactivating a tumor suppressor, p53, may provide a link between inflammation and tumorigenesis.
Hudson
J D
JD
Unit of Cancer Biology, Institute of Child Health, London WC1N 1EH, United Kingdom.
Shoaibi
M A
MA
Maestro
R
R
Carnero
A
A
Hannon
G J
GJ
Beach
D H
DH
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002908:Chronic Disease; D005347:Fibroblasts / Q000502:physiology; D007249:Inflammation / Q000150:complications*; D008263:Macrophage Migration-Inhibitory Factors / Q000494:pharmacology*; D051379:Mice; D009369:Neoplasms / Q000209:etiology*; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000502:physiology
D008263:Macrophage Migration-Inhibitory Factors; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide