Hypoxic condition- and high cell density-induced expression of Redd1 is regulated by activation of hypoxia-inducible factor-1alpha and Sp1 through the phosphatidylinositol 3-kinase/Akt signaling pathway.
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Jin HO, An S, Lee HC, Woo SH, Seo SK, Choe TB, Yoo DH, Lee SB, Um HD, Lee SJ, Park MJ, Kim JI, Hong SI, Rhee CH, Park IC
Hypoxic condition- and high cell density-induced expression of Redd1 is regulated by activation of hypoxia-inducible factor-1alpha and Sp1 through the phosphatidylinositol 3-kinase/Akt signaling pathway.
Cell Signal. 2007 Jul;19(7):1393-403. Epub 2007 Jan 20.
- PubMed ID
- 17307335 [ View in PubMed]
- Abstract
Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. In the present study, we demonstrated that the expression of Redd1 in response to hypoxia (1% O(2)), hypoxia-mimetic agent, cobalt chloride (CoCl(2)) and high cell density (HCD) requires coactivation of HIF-1alpha and Sp1. CoCl(2) and HCD induced the activation of HIF-1alpha and Sp1 in HeLa cells, and siRNAs targeting HIF-1alpha and Sp1 abrogated Redd1 expression. Inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 and by a dominant-negative PI3K mutant reduced the expression of Redd1 and activation of HIF-1alpha and Sp1 by CoCl(2) and HCD. Also, suppression of Akt activation blocked the expression of Redd1 and the activation of HIF-1alpha and Sp1 by CoCl(2) and HCD. Furthermore, we found that the induction of Redd1 expression by CoCl(2) can be mediated by activation of Sp1 in HIF-1alpha-deficient cells but that a higher level of Redd1 expression is achieved when these cells are transfected with HIF-1alpha. These results demonstrate that hypoxic condition-and HCD-induced expression of Redd1 is mediated by coactivation of Sp1 and HIF-1alpha downstream of the PI3K/Akt signaling pathway.
DrugBank Data that Cites this Article
- Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome LY-294002 Experimental DDIT4 54541 downregulated 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one results in decreased expression of DDIT4 mRNA 10q22.1 Oxygen Approved Vet Approved DDIT4 54541 upregulated Oxygen deficiency results in increased expression of DDIT4 mRNA 10q22.1 Oxygen Approved Vet Approved VEGFA 7422 upregulated Oxygen deficiency results in increased expression of VEGFA mRNA 6p21.1 - Pharmaco-proteomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Oxygen Approved Vet Approved HIF1A 3091 increased Oxygen deficiency results in increased expression of HIF1A protein 14q23.2 Oxygen Approved Vet Approved HIF1A 3091 increased Oxygen deficiency results in increased expression of HIF1A protein 14q23.2 Oxygen Approved Vet Approved HIF1A 3091 increased Oxygen deficiency results in increased expression of HIF1A protein 14q23.2 Oxygen Approved Vet Approved HIF1A 3091 increased Oxygen deficiency results in increased expression of HIF1A protein 14q23.2