Details

Autor(en) / Beteiligte

• Schmidt, Dirk
• Textor, Björn
• Pein, Oliver T
• Licht, Alexander H
• Andrecht, Sven
• Sator-Schmitt, Melanie
• Fusenig, Norbert E
• Angel, Peter
• Schorpp-Kistner, Marina

Titel

Critical role for NF-[kappa]B-induced JunB in VEGF regulation and tumor angiogenesis

Ist Teil von

• The EMBO journal, 2007-02, Vol.26 (3), p.710-719

Ort / Verlag

Heidelberg: Blackwell Publishing Ltd

Erscheinungsjahr

2007

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Regulation of vascular endothelial growth factor (VEGF) expression is a complex process involving a plethora of transcriptional regulators. The AP-1 transcription factor is considered as facilitator of hypoxia-induced VEGF expression through interaction with hypoxia-inducible factor (HIF) which plays a major role in mediating the cellular hypoxia response. As yet, both the decisive AP-1 subunit leading to VEGF induction and the molecular mechanism by which this subunit is activated have not been deciphered. Here, we demonstrate that the AP-1 subunit junB is a target gene of hypoxia-induced signaling via NF-kappaB. Loss of JunB in various cell types results in severely impaired hypoxia-induced VEGF expression, although HIF is present and becomes stabilized. Thus, we identify JunB as a critical independent regulator of VEGF transcription and provide a mechanistic explanation for the inherent vascular phenotypes seen in JunB-deficient embryos, ex vivo allantois explants and in vitro differentiated embryoid bodies. In support of these findings, tumor angiogenesis was impaired in junB(-/-) teratocarcinomas because of severely impaired paracrine-acting VEGF and the subsequent inability to efficiently recruit host-derived vessels.