title: Thymosin β4 stabilizes hypoxia-inducible factor-1α protein in an oxygen-independent manner.
abstract: The small actin-binding protein thymosin β4 (Tβ4) is understood to stimulate angiogenesis. Previously, we reported that Tβ4 induces angiogenesis by increasing vascular endothelial growth factor (VEGF) expression, but the mechanism underlying how Tβ4 upregulates VEGF expression remain unknown. To identify the mechanism of VEGF induction by Tβ4, we measured VEGF promoter activity and analyzed the effect of Tβ4 on VEGF RNA stability. The Tβ4 peptide had no effect on either VEGF promoter activity or VEGF RNA stability. We focused on the possibility that Tβ4 may indirectly induce VEGF expression via hypoxia-inducible factor (HIF)-1α. We determined that Tβ4 increased the stability of HIF-1α protein under normoxic conditions. These data suggest that Tβ4 indirectly induces VEGF expression by increasing the protein stability of HIF-1α in an oxygen-independent manner.
authors.affiliation: Department of Parasitology and Genetics, Kosin University College of Medicine, Busan, South Korea.
authors.forename: Mee Sun
authors.initials: MS
authors.lastname: Ock
authors.forename: Kyoung Seob
authors.initials: KS
authors.lastname: Song
authors.forename: Hynda
authors.initials: H
authors.lastname: Kleinman
authors.forename: Hee-Jae
authors.initials: HJ
authors.lastname: Cha
mesh_terms: D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D020871:RNA Stability / Q000235:genetics; D013947:Thymosin / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D000099201:Thymosin beta(4)
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010100:Oxygen; D013947:Thymosin; D042461:Vascular Endothelial Growth Factor A; D000099201:Thymosin beta(4)