Ferredoxin reductase affects p53-dependent, 5-fluorouracil–induced apoptosis in colorectal cancer ce
Author: ["Paul M. Hwang","Fred Bunz","Jian Yu","Carlo Rago","Timothy A. Chan","Michael P. Murphy","Geoffry F. Kelso","Robin A. J. Smith","Kenneth W. Kinzler","Bert Vogelstein"]
Publication: Nature Medicine
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Abstract
Loss of p53 gene function, which occurs in most colon cancer cells, has been shown to abolish the apoptotic response to 5-fluorouracil (5-FU). To identify genes downstream of p53 that might mediate these effects, we assessed global patterns of gene expression following 5-FU treatment of isogenic cells differing only in their p53 status. The gene encoding mitochondrial ferredoxin reductase (protein, FR; gene, FDXR) was one of the few genes significantly induced by p53 after 5-FU treatment. The FR protein was localized to mitochondria and suppressed the growth of colon cancer cells when over-expressed. Targeted disruption of the FDXR gene in human colon cancer cells showed that it was essential for viability, and partial disruption of the gene resulted in decreased sensitivity to 5-FU-induced apoptosis. These data, coupled with the effects of pharmacologic inhibitors of reactive oxygen species, indicate that FR contributes to p53-mediated apoptosis through the generation of oxidative stress in mitochondria.
Cite this article
Hwang, P., Bunz, F., Yu, J. et al. Ferredoxin reductase affects p53-dependent, 5-fluorouracil–induced apoptosis in colorectal cancer cells. Nat Med 7, 1111–1117 (2001). https://doi.org/10.1038/nm1001-1111
