Journal
CANCER CELL
Volume 11, Issue 5, Pages 407-420Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2007.04.001
Keywords
-
Categories
Funding
- NCI NIH HHS [P50 CA 103175, R37 CA 51497] Funding Source: Medline
Ask authors/readers for more resources
Many cancer cells are characterized by increased glycolysis and decreased respiration, even under aerobic conditions. The molecular mechanisms underlying this metabolic reprogramming are unclear. Here we show that hypoxia-inducible factor 1 (HIF-1) negatively regulates mitochondrial biogenesis and O-2 consumption in renal carcinoma cells lacking the von Hippel-Lindau tumor suppressor (VHL). HIF-1 mediates these effects by inhibiting C-MYC activity via two mechanisms. First, HIF-1 binds to and activates transcription of the MXI1 gene, which encodes a repressor of C-MYC transcriptional activity. Second, HIF-1 promotes MXI-1-independent, proteasome-dependent degradation of C-MYC. We demonstrate that transcription of the gene encoding the coactivator PGC-1 beta is C-MYC dependent and that loss of PGC-1 beta expression is a major factor contributing to reduced respiration in VHL-deficient renal carcinoma cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available