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VHL and p53: tumor suppressors team up to prevent cancer 总被引:2,自引:0,他引:2
Semenza GL 《Molecular cell》2006,22(4):437-439
In a recent issue of Molecular Cell, Roe et al. (2006) report that the von Hippel-Lindau (VHL) protein is a positive regulator of p53, thus providing insight into the mechanisms by which VHL loss of function leads to cancer. 相似文献
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Semenza GL 《Trends in molecular medicine》2001,7(8):345-350
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Oda S Oda T Nishi K Takabuchi S Wakamatsu T Tanaka T Adachi T Fukuda K Semenza GL Hirota K 《PloS one》2008,3(5):e2215
Background
Macrophage migration inhibitory factor (MIF) is not only a cytokine which has a critical role in several inflammatory conditions but also has endocrine and enzymatic functions. MIF is identified as an intracellular signaling molecule and is implicated in the process of tumor progression, and also strongly enhances neovascularization. Overexpression of MIF has been observed in tumors from various organs. MIF is one of the genes induced by hypoxia in an hypoxia-inducible factor 1 (HIF-1)-dependent manner.Methods/Principal Findings
The effect of MIF on HIF-1 activity was investigated in human breast cancer MCF-7 and MDA-MB-231 cells, and osteosarcoma Saos-2 cells. We demonstrate that intracellular overexpression or extracellular administration of MIF enhances activation of HIF-1 under hypoxic conditions in MCF-7 cells. Mutagenesis analysis of MIF and knockdown of 53 demonstrates that the activation is not dependent on redox activity of MIF but on wild-type p53. We also indicate that the MIF receptor CD74 is involved in HIF-1 activation by MIF at least when MIF is administrated extracellularly.Conclusion/Significance
MIF regulates HIF-1 activity in a p53-dependent manner. In addition to MIF''s potent effects on the immune system, MIF is linked to fundamental processes conferring cell proliferation, cell survival, angiogenesis, and tumor invasiveness. This functional interdependence between MIF and HIF-1α protein stabilization and transactivation activity provide a molecular mechanism for promotion of tumorigenesis by MIF. 相似文献26.
Liu L Marti GP Wei X Zhang X Zhang H Liu YV Nastai M Semenza GL Harmon JW 《Journal of cellular physiology》2008,217(2):319-327
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