Hypoxic condition- and high cell density-induced expression of Redd1 is regulated by activation of hypoxia-inducible factor-1α and Sp1 through the phosphatidylinositol 3-kinase/Akt signaling pathway

作者: Hyeon-Ok Jin , Sungkwan An , Hyung-Chahn Lee , Sang-Hyeok Woo , Sung-Keum Seo

DOI: 10.1016/J.CELLSIG.2006.12.014

关键词:

摘要: Abstract Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and DNA damage p53/p63; however, the signaling pathway which its expression induced has not been elucidated. In present study, we demonstrated that of Redd1 in response to (1% O 2 ), hypoxia-mimetic agent, cobalt chloride (CoCl ) high cell density (HCD) requires coactivation HIF-1α Sp1. CoCl HCD activation Sp1 HeLa cells, siRNAs targeting abrogated expression. Inhibition phosphatidylinositol 3-kinase (PI3K) LY294002 dominant-negative PI3K mutant reduced HCD. Also, suppression Akt blocked Furthermore, found induction can be mediated HIF-1α-deficient cells but higher level achieved when these are transfected with HIF-1α. These results demonstrate hypoxic condition-and HCD-induced downstream PI3K/Akt pathway.

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