Activation of Sp1-mediated Vascular Permeability Factor/Vascular Endothelial Growth Factor Transcription Requires Specific Interaction with Protein Kinase C ζ

• DOI: 10.1074/jbc.273.41.26277
• Publication Date: 2002-07-26T15:02:22Z
• Authors: Soumitro Pal; Kevin P. Claffey; Herbert T. Cohen; Debabrata Mukhopa...
• Keywords: Vascular permeability; Sp1 transcription factor

The transcription factor Sp1 is ubiquitously expressed and plays a significant role in the constitutive induced expression of variety mammalian genes may even contribute to tumorigenesis. Here, we describe novel pathway whereby promotes vascular permeability factor/vascular endothelial growth (VPF/VEGF), potent angiogenic factor, by interacting directly specifically with protein kinase C zeta (PKC zeta) isoform renal cell carcinoma. PKC binds phosphorylates zinc finger region Sp1. Moreover, presence wild type von Hippel-Lindau gene product, interaction inhibited, this manner steady state levels phosphorylation are decreased significantly. Co-transfection carcinoma cells human fibrosarcoma plasmid overexpressing VPF/VEGF promoter luciferase constructs results activation Sp1-mediated transcription, whereas dominant-negative mutant repressed activation. Taken together, our suggest new signaling through provide an insight into Sp1-dependent transcriptional regulation thus tumor angiogenesis.