Cited by 649Macrophage Migration Inhibitory FactorCancer-related Molecular PathwaysMechanisms of cancer metastasis

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A Proinflammatory Cytokine Inhibits P53 Tumor Suppressor Activity

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Hudson, James D., Shoaibi, Mahmood A., Maestro, Roberta, Carnero, Amancio, Hannon, Gregory J., Beach, David H.·1999·The Journal of Experimental Medicine

DOI 10.1084/jem.190.10.1375PMC PMC2195698

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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.

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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)
ORCID: Maestro, Roberta
Carnero, Amancio
Hannon, Gregory J.
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
DOI: 10.1084/jem.190.10.1375
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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A Proinflammatory Cytokine Inhibits P53 Tumor Suppressor Activity

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