Complex role of protein phosphorylation in gene activation by hypoxia

MAPK Signaling Up-regulates the Activity of Hypoxia-inducible Factors by Its Effects on p300

“…It was later shown that PDx, a MEK-specific inhibitor, suppressed hypoxia-stimulated HIF activity but had little effect on the formation of HIF DNA-binding complex (30). These results suggested that MAPK signaling might play a role in the regulation of the transactivation activity of HIF-1 but had an insignificant effect on the protein levels of HIF-1␤ and hypoxiastimulated accumulation of HIF-1␣.…”

“…Previously, we also found that in B1 cells, genistein inhibited HIF-1 activity and gene expression in response to hypoxic stimulation (30). However, PDx, a selective MEK inhibitor (41), inhibited hypoxia-stimulated gene expression but had little effect on HIF-1␣ level and the formation of DNA binding complex (30). Here, we investigated further the role of MAPK signaling in basal and induced activity of HIF-1␣ in B1 cells.…”

“…It has been observed that genistein, a tyrosine kinase inhibitor, decreased the protein levels of both HIF-1␣ and HIF-1␤ and inhibited the formation of DNA binding complex (40). Previously, we also found that in B1 cells, genistein inhibited HIF-1 activity and gene expression in response to hypoxic stimulation (30). However, PDx, a selective MEK inhibitor (41), inhibited hypoxia-stimulated gene expression but had little effect on HIF-1␣ level and the formation of DNA binding complex (30).…”

Role of HIF-1α and VEGF in human mesenchymal stem cell proliferation by 17β-estradiol: involvement of PKC, PI3K/Akt, and MAPKs

“…As a general rule, the primary action of E 2 is mediated by ERs. In addition, conventional ERs are transcription factors regulating gene expression, and these mechanisms may be mediated by a complex system of interacting signal molecules in various cell types (10,15,19,20,30). Moreover, current evidence indicates that the small population of ER␣ and ER␤ is localized within the plasma mem- Ϫ6 M Akt inhibitor before 12-h E2 treatment.…”

The Involvement of the ERK-Hypoxia-Angiogenesis Signaling Axis and HIF-1 in Hepatocellular Carcinoma

“…This was shown by the use of MEK1 inhibitor PD98059 which decreased HIF-1-dependent gene expression in a number of cell lines including the hepatoma-derived Hep3B (Minet et al, 2000;Salceda et al, 1997). Also, studies from our own and other groups using Gal4-HIF-1 fusion proteins have shown that the ERK pathway is involved in hypoxia-dependent HIF-1 transactivation domain function in different cell lines Mylonis et al, 2006).…”