The execution of the transcriptional axis mutant p53, E2F1 and ID4 promotes tumor neo-angiogenesis Journal Articles uri icon

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  • ID4 (inhibitor of DNA binding 4) is a member of a family of proteins that function as dominant-negative regulators of basic helix-loop-helix transcription factors. Growing evidence links ID proteins to cell proliferation, differentiation and tumorigenesis. Here we identify ID4 as a transcriptional target of gain-of-function p53 mutants R175H, R273H and R280K. Depletion of mutant p53 protein severely impairs ID4 expression in proliferating tumor cells. The protein complex mutant p53-E2F1 assembles on specific regions of the ID4 promoter and positively controls ID4 expression. The ID4 protein binds to and stabilizes mRNAs encoding pro-angiogenic factors IL8 and GRO-alpha. This results in the increase of the angiogenic potential of cancer cells expressing mutant p53. These findings highlight the transcriptional axis mutant p53, E2F1 and ID4 as a still undefined molecular mechanism contributing to tumor neo-angiogenesis.


  • Fontemaggi, Giulia
  • Dell'Orso, Stefania
  • Trisciuoglio, Daniela
  • Shay, Tal
  • Melucci, Elisa
  • Fazi, Francesco
  • Terrenato, Irene
  • Mottolese, Marcella
  • Muti, Paola
  • Domany, Eytan
  • Del Bufalo, Donatella
  • Strano, Sabrina
  • Blandino, Giovanni

publication date

  • October 2009

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