A proinflammatory cytokine inhibits p53 tumor suppressor activity

Hudson, J. D., Shoaibi, M. A., Maestro, R., Carnero, A., Hannon, G. J., Beach, D. H. (1999) A proinflammatory cytokine inhibits p53 tumor suppressor activity. Journal of Experimental Medicine, 190 (10). pp. 1375-1382. ISSN 00221007 (ISSN)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/10562313
DOI: 10.1084/jem.190.10.1375

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.

Item Type: Paper
Uncontrolled Keywords: Apoptosis Growth arrest Inflammation and cancer Macrophage migration inhibitory factor p53 cytokine macrophage migration inhibition factor protein p53 animal cell article cancer inhibition carcinogenesis cell proliferation genetic stability growth disorder inflammation nonhuman priority journal regulatory mechanism transactivation Animals Cell Line Chronic Disease Fibroblasts Macrophage Migration-Inhibitory Factors Mice Neoplasms Nitric Oxide Rats Trans-Activation (Genetics) Tumor Suppressor Protein p53
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
diseases & disorders > inflammation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > suppressor
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: Matt Covey
Date: 1999
Date Deposited: 09 Jan 2013 17:33
Last Modified: 09 Jan 2013 17:33
PMCID: PMC2195698
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26478

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