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.

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; Fazi, Francesco; Irene, Terrenato; Marcella, Mottolese; Paola, Muti; Eytan, Domany; Donatella Del, Bufalo; Sabrina, Strano; Giovanni, Blandino. - In: NATURE STRUCTURAL & MOLECULAR BIOLOGY. - ISSN 1545-9993. - STAMPA. - 16:10(2009), pp. 1086-1093. [10.1038/nsmb.1669]

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

FAZI, Francesco;
2009

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.
2009
01 Pubblicazione su rivista::01a Articolo in rivista
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; Fazi, Francesco; Irene, Terrenato; Marcella, Mottolese; Paola, Muti; Eytan, Domany; Donatella Del, Bufalo; Sabrina, Strano; Giovanni, Blandino. - In: NATURE STRUCTURAL & MOLECULAR BIOLOGY. - ISSN 1545-9993. - STAMPA. - 16:10(2009), pp. 1086-1093. [10.1038/nsmb.1669]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/139596
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