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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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-α. 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.

Original languageEnglish
Pages (from-to)1086-1093
Number of pages8
JournalNature Structural and Molecular Biology
Volume16
Issue number10
DOIs
Publication statusPublished - Oct 2009

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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