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• W2099656411 abstract "ABSTRACT Hypoxia and anoxia are important microenvironmental stresses that contribute to pathological events such as solid-tumor development. We have been investigating the effects of hypoxia and anoxia on expression of the proto-oncogene c- jun and the regulation of c-Jun/AP-1 transcription factors. In earlier work using genetically manipulated mouse embryo fibroblasts (mEFs), we found a functional relationship among c- jun expression, c-Jun N-terminal phosphorylation, and the presence of hypoxia-inducible factor 1α (HIF-1α), the oxygen-regulated subunit of the HIF-1 transcription factor. Both the induction of c- jun mRNA expression and c-Jun N-terminal phosphorylation in cells exposed to hypoxia or anoxia were found to be dependent on the presence of HIF-1α, but this was not the case in cells exposed to less-severe hypoxia. Here we describe new findings concerning HIF-1-dependent c-Jun N-terminal phosphorylation in cells exposed to hypoxia or anoxia. Specifically, we report that hypoxia-inducible c-Jun N-terminal kinase (JNK) activity, which involves JNKs or stress-activated protein kinases (SAPKs), is dependent on enhanced glucose utilization mediated by HIF-1. These results suggest a model in which hypoxia-inducible JNK activity is connected to oxygen sensing through increased glucose absorption and/or glycolytic activity regulated by the HIF-1 system. We also found that basal threonine and tyrosine phosphorylation (within the TEY motif) of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and the corresponding ERK1/2 activity were defective in hypoxic HIF-1α-null mEFs but not in wild-type mEFs, independently of glucose uptake. Therefore, the activities of both JNKs/SAPKs and ERK1/2 are sensitive to HIF-1-dependent processes in cells exposed to hypoxia or anoxia." @default.
• W2099656411 created "2016-06-24" @default.
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• W2099656411 date "2004-05-01" @default.
• W2099656411 modified "2023-10-11" @default.
• W2099656411 title "Glucose Utilization Is Essential for Hypoxia-Inducible Factor 1α-Dependent Phosphorylation of c-Jun" @default.
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• W2099656411 doi "https://doi.org/10.1128/mcb.24.10.4128-4137.2004" @default.
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