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 journalArticle

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

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DNA
Neoplasms
Mutant Proteins
Basic Helix-Loop-Helix Transcription Factors
Angiogenesis Inducing Agents
DNA-Binding Proteins
Interleukin-8
Cell Differentiation
Carcinogenesis
Cell Proliferation
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

The execution of the transcriptional axis mutant p53, E2F1 and ID4 promotes 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.

In: Nature Structural and Molecular Biology, Vol. 16, No. 10, 10.2009, p. 1086-1093.

Research output: Contribution to journalArticle

Fontemaggi, G, Dell'Orso, S, Trisciuoglio, D, Shay, T, Melucci, E, Fazi, F, Terrenato, I, Mottolese, M, Muti, P, Domany, E, Del Bufalo, D, Strano, S & Blandino, G 2009, 'The execution of the transcriptional axis mutant p53, E2F1 and ID4 promotes tumor neo-angiogenesis', Nature Structural and Molecular Biology, vol. 16, no. 10, pp. 1086-1093. https://doi.org/10.1038/nsmb.1669
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. / The execution of the transcriptional axis mutant p53, E2F1 and ID4 promotes tumor neo-angiogenesis. In: Nature Structural and Molecular Biology. 2009 ; Vol. 16, No. 10. pp. 1086-1093.
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