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- W2018304885 abstract "The transcription factor Sp1 is ubiquitously expressed and plays a significant role in the constitutive and induced expression of a variety of mammalian genes and may even contribute to tumorigenesis. Here, we describe a novel pathway whereby Sp1 promotes the transcription of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), a potent angiogenic factor, by interacting directly and specifically with protein kinase C ζ (PKC ζ) isoform in renal cell carcinoma. PKC ζ binds and phosphorylates the zinc finger region of Sp1. Moreover, in the presence of the wild type von Hippel-Lindau gene product, the interaction of Sp1 with PKC ζ is inhibited, and in this manner steady state levels of Sp1 phosphorylation are decreased significantly. Co-transfection of renal cell carcinoma cells and human fibrosarcoma cells with a plasmid overexpressing PKC ζ and VPF/VEGF promoter luciferase constructs results in activation of Sp1-mediated transcription, whereas expression of a dominant-negative mutant of PKC ζ repressed this activation. Taken together, our results suggest a new pathway of cell signaling through PKC ζ and provide an insight into PKC ζ and Sp1-dependent transcriptional regulation of VPF/VEGF expression and thus tumor angiogenesis." @default.
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- W2018304885 date "1998-10-01" @default.
- W2018304885 modified "2023-10-13" @default.
- W2018304885 title "Activation of Sp1-mediated Vascular Permeability Factor/Vascular Endothelial Growth Factor Transcription Requires Specific Interaction with Protein Kinase C ζ" @default.
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- W2018304885 doi "https://doi.org/10.1074/jbc.273.41.26277" @default.
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