The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
p53 Activation in Adipocytes of Obese Mice
Open accessAbstract
The tumor suppressor p53 is a transcription factor that activates or represses its target genes after various genotoxic stresses. We have previously shown that sterol regulatory element-binding protein-1 (SREBP-1), a key transcriptional regulator of triglyceride synthesis, and the lipogenic enzymes under its control are markedly suppressed in adipocytes from genetically obese ob/ob mice. Here we demonstrate that p53 and its target genes are highly induced in adipocytes of ob/ob mice in a fed state, leading to the negative regulation of SREBP-1 and thereby lipogenic genes. In fact, disruption of p53 in ob/ob mice completely suppressed the p53-regulated genes to wild-type levels and partially restored expression of lipogenic enzymes. Consistently, reporter gene analysis showed that p53 overexpression suppressed the promoter activity of the SREBP-1c gene and its downstream genes. Thus, the activation of p53 might constitute a negative feedback loop against excess fat accumulation in adipocytes. In conclusion, we discovered a novel role of p53 in the pathophysiology of obesity.
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Cites
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092
p53 mutant mice that display early ageing-associated phenotypes
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Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis
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OBESE, A NEW MUTATION IN THE HOUSE MOUSE*
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Akt Enhances Mdm2-mediated Ubiquitination and Degradation of p53
Ogawara, Y., Kishishita, S., Obata, T., Isazawa, Y., Suzuki, T., Tanaka, K., Masuyama, N., & Gotoh, Y. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109745200 · Cited by 617
The expression of adipogenic genes is decreased in obesity and diabetes mellitus
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Specific repression of TATA-mediated but not initiator-mediated transcription by wild-type p53
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Cited by
Mutant p53 disrupts mammary tissue architecture via the mevalonate pathway
Freed-Pastor, W. A., Mizuno, H., Zhao, X., Langerød, A., Moon, S.-H., Rodriguez-Barrueco, R., Barsotti, A., Chicas, A., Li, W., Polotskaia, A., et al. (2012) · Cell · doi:10.1016/j.cell.2011.12.017 · Cited by 865
Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention
Butler, L. M., Perone, Y., Dehairs, J., Lupien, L. E., de Laat, V., Talebi, A., Loda, M., Kinlaw, W. B., & Swinnen, J. V. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.07.013 · Cited by 589
Obesity and related consequences to ageing
Jura, M., & Kozak, L. P. (2016) · AGE · doi:10.1007/s11357-016-9884-3 · Cited by 473
Lim, Y.-M., Lim, H., Hur, K. Y., Quan, W., Lee, H.-Y., Cheon, H., Ryu, D., Koo, S.-H., Kim, H. L., Kim, J., et al. (2014) · Nature Communications · doi:10.1038/ncomms5934 · Cited by 189
Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF-targeted therapy
Talebi, A., Dehairs, J., Rambow, F., Rogiers, A., Nittner, D., Derua, R., Vanderhoydonc, F., Duarte, J. A. G., Bosisio, F., Van den Eynde, K., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04664-0 · Cited by 155
Metadata
- Authors
- Yahagi, N., Shimano, H., Matsuzaka, T., Najima, Y., Sekiya, M., Nakagawa, Y., Ide, T., Tomita, S., Okazaki, H., Tamura, Y., Iizuka, Y., Ohashi, K., Gotoda, T., Nagai, R., Kimura, S., Ishibashi, S., Osuga, J.-I., & Yamada, N.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-07
- Volume
- 278
- Issue
- 28
- Pages
- 25395-25400
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2142252299
- Cited by
- 220
- References
- 8
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Yahagi, N., Shimano, H., Matsuzaka, T., Najima, Y., Sekiya, M., Nakagawa, Y., Ide, T., Tomita, S., Okazaki, H., Tamura, Y., Iizuka, Y., Ohashi, K., Gotoda, T., Nagai, R., Kimura, S., Ishibashi, S., Osuga, J.-I., & Yamada, N. (2003). p53 Activation in Adipocytes of Obese Mice. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m302364200
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