An essential role for p300/CBP in the cellular response to hypoxia

• Zoltàn Arany

  The Dana–Farber Cancer Institute and Harvard Medical School, Boston, MA 02115; and Division of Hematology, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115

• L. Eric Huang

  The Dana–Farber Cancer Institute and Harvard Medical School, Boston, MA 02115; and Division of Hematology, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115

• Richard Eckner

  The Dana–Farber Cancer Institute and Harvard Medical School, Boston, MA 02115; and Division of Hematology, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115

• Shoumo Bhattacharya

  The Dana–Farber Cancer Institute and Harvard Medical School, Boston, MA 02115; and Division of Hematology, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115

• Chian Jiang

  The Dana–Farber Cancer Institute and Harvard Medical School, Boston, MA 02115; and Division of Hematology, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115

• Mark A. Goldberg

  The Dana–Farber Cancer Institute and Harvard Medical School, Boston, MA 02115; and Division of Hematology, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115

• H. Franklin Bunn

  The Dana–Farber Cancer Institute and Harvard Medical School, Boston, MA 02115; and Division of Hematology, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115

• David M. Livingston

  The Dana–Farber Cancer Institute and Harvard Medical School, Boston, MA 02115; and Division of Hematology, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115

抄録

p300 and CBP are homologous transcription adapters targeted by the E1A oncoprotein. They participate in numerous biological processes, including cell cycle arrest, differentiation, and transcription activation. p300 and/or CBP (p300/CBP) also coactivate CREB. How they participate in these processes is not yet known. In a search for specific p300 binding proteins, we have cloned the intact cDNA for HIF-1α. This transcription factor mediates hypoxic induction of genes encoding certain glycolytic enzymes, erythropoietin (Epo), and vascular endothelial growth factor. Hypoxic conditions lead to the formation of a DNA binding complex containing both HIF-1α and p300/CBP. Hypoxia-induced transcription from the Epo promoter was specifically enhanced by ectopic p300 and inhibited by E1A binding to p300/CBP. Hypoxia-induced VEGF and Epo mRNA synthesis were similarly inhibited by E1A. Hence, p300/CBP–HIF complexes participate in the induction of hypoxia-responsive genes, including one (vascular endothelial growth factor) that plays a major role in tumor angiogenesis. Paradoxically, these data, to our knowledge for the first time, suggest that p300/CBP are active in both transformation suppression and tumor development.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 93 (23), 12969-12973, 1996-11-12

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1361137045166382208
• NII論文ID: 80009344514
• DOI: 10.1073/pnas.93.23.12969
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.93.23.12969
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