共查询到20条相似文献,搜索用时 15 毫秒
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Leu-574 of HIF-1alpha is essential for the von Hippel-Lindau (VHL)-mediated degradation pathway 总被引:3,自引:0,他引:3
Huang LE Pete EA Schau M Milligan J Gu J 《The Journal of biological chemistry》2002,277(44):41750-41755
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In a recent issue of Molecular Cell, Li et al. (2007) reported that ionizing radiation stabilizes hypoxia-inducible factor 1alpha (HIF-1alpha) in normoxic tumor tissues through S-nitrosylation by nitric oxide (NO) generated from neighboring activated macrophages. 相似文献
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The hypoxia-inducible factor-1 (HIF-1) is the master regulator of the cellular response to hypoxia and its expression levels are tightly controlled through synthesis and degradation. It is widely accepted that HIF-1alpha protein accumulation during hypoxia results from inhibition of its oxygen-dependent degradation by the von Hippel Lindau protein (pVHL) pathway. However, recent data describe new pVHL- or oxygen-independent mechanisms for HIF-1alpha degradation. Furthermore, the hypoxia-induced increase in HIF-1alpha levels is facilitated by the continued translation of HIF-1alpha during hypoxia despite the global inhibition of protein translation. Recent work has contributed to an increased understanding of the mechanisms that control the translation and degradation of HIF-1alpha under both normoxic and hypoxic conditions. 相似文献
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Wang F Sekine H Kikuchi Y Takasaki C Miura C Heiwa O Shuin T Fujii-Kuriyama Y Sogawa K 《Biochemical and biophysical research communications》2002,295(3):657-662
We have investigated inhibitory mechanisms of hypoxic activation of HIF-1alpha by nitric oxide (NO). Using a Hep3B cell-derived cell line, HRE7 cells, we found that the inhibition of HIF-1alpha activity by NO requires a substantial amount of oxygen, albeit at a lower level. We further investigated the effect of NO on the binding activity of the von Hippel-Lindau tumor suppressor protein (pVHL) to the N-terminal activation domain (NAD) overlapping the oxygen-dependent degradation domain (ODD) of HIF-1alpha, because this reaction involves prolyl hydroxylation in NAD that requires oxygen. Although we could not detect any binding activity when NAD was incubated with whole cell extracts from cells treated with CoCl(2) or desferrioxamine, the binding capacity was manifested when Hep3B cells were treated together with NO. This activation was also observed when whole cell extracts from CoCl(2)-treated cells were incubated with NO. The prolyl hydroxylase from Hep3B cells treated with CoCl(2) was partially purified about 80-fold, and several enzymatic properties were examined. The enzyme required ferrous ion and 2-oxoglutaric acid. Strong activation of the prolyl hydroxylase by NO was observed without further addition of ferrous ion. 相似文献
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HIF-1 and mechanisms of hypoxia sensing 总被引:37,自引:0,他引:37
Semenza GL 《Current opinion in cell biology》2001,13(2):167-171
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