Che-1 Promotes Tumor Cell Survival by Sustaining Mutant p53 Transcription and Inhibiting DNA Damage Response Activation

被引：48

作者：

Bruno, Tiziana ^{[1
]}

Desantis, Agata ^{[1
,5
]}

Bossi, Gianluca ^{[3
]}

Di Agostino, Silvia ^{[1
]}

Sorino, Cristina ^{[1
,5
]}

De Nicola, Francesca ^{[1
]}

Iezzi, Simona ^{[1
,2
,5
]}

Franchitto, Annapaola ^{[6
]}

Benassi, Barbara ^{[1
]}

Galanti, Sergio ^{[1
]}

La Rosa, Francesca ^{[1
]}

Floridi, Aristide ^{[5
]}

Bellacosa, Alfonso ^{[1
,7
]}

Passananti, Claudio ^{[2
,4
]}

Blandino, Giovanni ^{[1
,2
]}

Fanciulli, Maurizio ^{[1
,2
]}

机构：

[1] Regina Elena Inst Canc Res, Dept Therapeut Programs Dev, Lab B, I-00144 Rome, Italy

[2] Regina Elena Inst Canc Res, Rome Oncogenom Ctr, I-00144 Rome, Italy

[3] Regina Elena Inst Canc Res, Dept Expt Oncol, Mol Oncogenesis Lab, I-00158 Rome, Italy

[4] Regina Elena Inst Canc Res, CNR, Ist Biol & Patol Mol, I-00158 Rome, Italy

[5] Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy

[6] Ist Super Sanita, Dept Environm & Primary Prevent, Genome Stabil Grp, I-00161 Rome, Italy

[7] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA

来源：

CANCER CELL | 2010年 / 18卷 / 02期

关键词：

P73 INDUCES APOPTOSIS; GENOMIC INSTABILITY; IN-VIVO; GAIN; PHOSPHORYLATION; CHECKPOINT; CANCER; INTERACTS; GROWTH; BREAKS;

D O I：

10.1016/j.ccr.2010.05.027

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Che-1 is a RNA polymerase II binding protein involved in the regulation of gene transcription and, in response to DNA damage, promotes p53 transcription. In this study, we investigated whether Che-1 regulates mutant p53 expression. We found that Che-1 is required for sustaining mutant p53 expression in several cancer cell lines, and that Che-1 depletion by siRNA induces apoptosis both in vitro and in vivo. Notably, loss of Che-1 activates DNA damage checkpoint response and induces transactivation of p73. Therefore, these findings underline the important role that Che-1 has in survival of cells expressing mutant p53.

引用

页码：122 / 134

页数：13

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