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A Proinflammatory Cytokine Inhibits P53 Tumor Suppressor Activity
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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.
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“MIF is a potent cytokine that overcomes p53 function by suppressing its transcriptional activity33.”
From Inflammation and cancer (2002) · cites this paper as [33]
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“tetracycline regulated expression of wild-type p53 (GFP tagged) in the TGP53-4 mouse cell line (27) caused a significant decline in endogenous PGM activity (Fig. 5B).”
From Glycolytic Enzymes Can Modulate Cellular Life Span (2005) · cites this paper as [27]
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Metadata
- Authors
- Hudson, J. D., Shoaibi, M. A., Maestro, R., Carnero, A., Hannon, G. J., & Beach, D. H.
- Affiliations
- aUnit of Cancer Biology, Institute of Child Health, London WC1N 1EH, United Kingdom
- Centro di Riferimento Oncologico (IT)
- Cold Spring Harbor Laboratory (US)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1999-11-15
- Volume
- 190
- Issue
- 10
- Pages
- 1375-1382
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2195698
- OpenAlex
- W2110929110
- Cited by
- 649
- References
- 48
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 14 · 2023: 10 · 2022: 12 · 2021: 18 · 2020: 25 · 2019: 17 · 2018: 14 · 2017: 14 · 2016: 27 · 2015: 24 · 2014: 25 · 2013: 25 · 2012: 38
- FWCI
- 9.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, other-oa)
- Funders
- University College London
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Macrophage Migration Inhibitory Factor
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- p53, macrophage migration inhibitory factor, inflammatory cytokines, tumor suppressor inactivation, inflammation and tumorigenesis, p53 transcriptional activation, apoptosis, cell proliferation, genome stability
- MeSH terms
- Animals, Cell Line, Chronic Disease, Fibroblasts, Inflammation, Macrophage Migration-Inhibitory Factors, Neoplasms, Nitric Oxide, Transcriptional Activation, Tumor Suppressor Protein p53, Apoptosis, Mice, Rats
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