The execution of the transcriptional axis mutant p53, E2F1 and ID4 promotes tumor neo-angiogenesis
Articolo
Data di Pubblicazione:
2009
Citazione:
The execution of the transcriptional axis mutant p53, E2F1 and ID4 promotes tumor neo-angiogenesis / G. Fontemaggi, S. Dell'Orso, D. Trisciuoglio, T. Shay, E. Melucci, F. Fazi, I. Terrenato, M. Mottolese, P. Muti, E. Domany, D. Del Bufalo, S. Strano, G. Blandino. - In: NATURE STRUCTURAL & MOLECULAR BIOLOGY. - ISSN 1545-9993. - 16:10(2009), pp. 1086-1093. [10.1038/nsmb.1669]
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cytokines; E2F1 Transcription Factor; Humans; Inhibitor of Differentiation Proteins; Interleukin-8; Microcirculation; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A; Gene Expression Regulation, Neoplastic; Mutation; Neovascularization, Pathologic; Transcription, Genetic
Elenco autori:
G. Fontemaggi, S. Dell'Orso, D. Trisciuoglio, T. Shay, E. Melucci, F. Fazi, I. Terrenato, M. Mottolese, P. Muti, E. Domany, D. Del Bufalo, S. Strano, G. Blandino
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