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

被引：155

作者：

Fontemaggi, Giulia ^{[1
,2
,3
]}

Dell'Orso, Stefania ^{[1
,2
]}

Trisciuoglio, Daniela ^{[4
]}

Shay, Tal ^{[5
]}

Melucci, Elisa ^{[6
]}

Fazi, Francesco ^{[7
,8
]}

Terrenato, Irene ^{[9
]}

Mottolese, Marcella ^{[6
]}

Muti, Paola ^{[9
]}

Domany, Eytan ^{[5
]}

Del Bufalo, Donatella ^{[4
]}

Strano, Sabrina ^{[1
,10
]}

Blandino, Giovanni ^{[1
,2
]}

机构：

[1] Regina Elena Inst Canc Res, Translat Oncogen Unit, Rome, Italy

[2] Regina Elena Inst Canc Res, ROC, Rome, Italy

[3] Univ Perugia, Dept Clin & Expt Med, Gen Pathol Sect, I-06100 Perugia, Italy

[4] Regina Elena Inst Canc Res, Expt Chemotherapy Lab, Rome, Italy

[5] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel

[6] Regina Elena Inst Canc Res, Dept Pathol, Rome, Italy

[7] Univ Roma La Sapienza, Dept Histol & Med Embryol, Rome, Italy

[8] San Raffaele Biomed Pk Fdn, Rome, Italy

[9] Regina Elena Inst Canc Res, Dept Epidemiol, Rome, Italy

[10] Regina Elena Inst Canc Res, Sci Direct, Mol Chemoprevent Grp, Rome, Italy

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2009年 / 16卷 / 10期

关键词：

LOOP-HELIX PROTEINS; CANCER-CELL-LINES; AU-RICH ELEMENTS; GAIN-OF-FUNCTION; GENE CONTRIBUTES; MESSENGER-RNA; BREAST-CANCER; EXPRESSION; GROWTH; CYCLE;

D O I：

10.1038/nsmb.1669

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1086 / U111

页数：9

共 52 条

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