The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
p53 is a suppressor of inflammatory response in mice
Abstract
Chronic inflammation is known to promote cancer, suggesting that negative regulation of inflammation is likely to be tumor suppressive. We found that p53 is a general inhibitor of inflammation that acts as an antagonist of nuclear factor κB (NFκB). We first observed striking similarities in global gene expression profiles in human prostate cancer cells LNCaP transduced with p53 inhibitory genetic element or treated with TNF, suggesting that p53 inhibits transcription of TNF‐inducible genes that are largely regulated by NFκB. Consistently, ectopically expressed p53 acts as an inhibitor of transcription of NFκB‐dependent promoters. Furthermore, suppression of inflammatory response by p53 was observed in vivo in mice by comparing wild‐type and p53 null animals at molecular (inhibition of transcription of genes encoding cytokines and chemokines, reducing accumulation of reactive oxygen species and protein oxidation products), cellular (activation of macrophages and neutrophil clearance) and organismal (high levels of metabolic markers of inflammation in tissues of p53‐deficient mice and their hypersensitivity to LPS) levels. These observations indicate that p53, acting through suppression of NFκB, plays the role of a general “buffer” of innate immune response in vivo that is well consistent with its tumor suppressor function and frequent constitutive activation of NFκB in tumors.
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Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649
Activators and target genes of Rel/NF-κB transcription factors
Pahl, H. L. (1999) · Oncogene · doi:10.1038/sj.onc.1203239 · Cited by 3,727
Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils
Eiserich, J. P., Hristova, M., Cross, C. E., Jones, A. D., Freeman, B. A., Halliwell, B., & van der Vliet, A. (1998) · Nature · doi:10.1038/34923 · Cited by 1,496
Transcriptional Cross Talk between NF-κB and p53
Webster, G. A., & Perkins, N. D. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3485 · Cited by 598
Kuwano, K., Kunitake, R., Kawasaki, M., Nomoto, Y., Hagimoto, N., Nakanishi, Y., & Hara, N. (1996) · American journal of respiratory and critical care medicine · doi:10.1164/ajrccm.154.2.8756825 · Cited by 339
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von der Thüsen, J. H., van Vlijmen, B. J. M., Hoeben, R. C., Kockx, M. M., Havekes, L. M., van Berkel, T. J. C., & Biessen, E. A. L. (2002) · Circulation · doi:10.1161/01.cir.0000015502.97828.93 · Cited by 203
Cited by
Inflammation and cancer: triggers, mechanisms, and consequences
Greten, F. R., & Grivennikov, S. I. (2019) · Immunity · doi:10.1016/j.immuni.2019.06.025 · Cited by 3,806
Reactive oxygen species and cancer paradox: To promote or to suppress?
Galadari, S., Rahman, A., Pallichankandy, S., & Thayyullathil, F. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.01.004 · Cited by 893
Salminen, A., Hyttinen, J. M. T., & Kaarniranta, K. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0748-0 · Cited by 866
Smoking and Lung Cancer: The Role of Inflammation
Walser, T., Cui, X., Yanagawa, J., Lee, J. M., Heinrich, E., Lee, G., Sharma, S., & Dubinett, S. M. (2008) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200809-100th · Cited by 379
p53, cancer and the immune response
Blagih, J., Buck, M. D., & Vousden, K. H. (2020) · Journal of Cell Science · doi:10.1242/jcs.237453 · Cited by 333
Metadata
- Authors
- Komarova, E. A., Krivokrysenko, V., Wang, K., Neznanov, N., Chernov, M. V., Komarov, P. G., Brennan, M., Golovkina, T. V., Rokhlin, O., Kuprash, D. V., Nedospasov, S. A., Hazen, S. R., Feinstein, E., & Gudkov, A. V.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2005-04-05
- Volume
- 19
- Issue
- 8
- Pages
- 1030-1032
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2127464082
- Cited by
- 247
- References
- 7
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- closed
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- Komarova, E. A., Krivokrysenko, V., Wang, K., Neznanov, N., Chernov, M. V., Komarov, P. G., Brennan, M., Golovkina, T. V., Rokhlin, O., Kuprash, D. V., Nedospasov, S. A., Hazen, S. R., Feinstein, E., & Gudkov, A. V. (2005). p53 is a suppressor of inflammatory response in mice. The FASEB Journal. https://doi.org/10.1096/fj.04-3213fje
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