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PMID:10562313

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Citation

Hudson, JD, Shoaibi, MA, Maestro, R, Carnero, A, Hannon, GJ and Beach, DH (1999) A proinflammatory cytokine inhibits p53 tumor suppressor activity. J. Exp. Med. 190:1375-82

Abstract

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.

Links

PubMed PMC2195698

Keywords

Animals; Apoptosis; Cell Line; Chronic Disease; Fibroblasts/physiology; Inflammation/complications; Macrophage Migration-Inhibitory Factors/pharmacology; Mice; Neoplasms/etiology; Nitric Oxide/physiology; Rats; Transcriptional Activation; Tumor Suppressor Protein p53/antagonists & inhibitors; Tumor Suppressor Protein p53/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:MIF

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:P53

involved_in

GO:0090343: positive regulation of cell aging

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MIF

involved_in

GO:0010629: negative regulation of gene expression

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MIF

involved_in

GO:0071157: negative regulation of cell cycle arrest

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MIF

involved_in

GO:0090344: negative regulation of cell aging

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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