Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation

Tiziana Bruno; Agata Desantis; Gianluca Bossi; Silvia Di Agostino; Cristina Sorino; Francesca De Nicola; Simona Iezzi; Annapaola Franchitto; Barbara Benassi; Sergio Galanti; Francesca La Rosa; Aristide Floridi; Alfonso Bellacosa; Claudio Passananti; Giovanni Blandino; Maurizio Fanciulli

doi:10.1016/j.ccr.2010.05.027

Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation

Tiziana Bruno, Agata Desantis, Gianluca Bossi, Silvia Di Agostino, Cristina Sorino, Francesca De Nicola, Simona Iezzi, Annapaola Franchitto, Barbara Benassi, Sergio Galanti, Francesca La Rosa, Aristide Floridi, Alfonso Bellacosa, Claudio Passananti, Giovanni Blandino, Maurizio Fanciulli

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	122-134
Number of pages	13
Journal	Cancer Cell
Volume	18
Issue number	2
DOIs	https://doi.org/10.1016/j.ccr.2010.05.027
State	Published - Aug 2010

Keywords

Animals
Apoptosis
Apoptosis Regulatory Proteins/genetics
Breast Neoplasms/genetics
Cell Line, Tumor
Cell Survival/physiology
DNA Damage
DNA Repair/physiology
DNA-Binding Proteins/genetics
Humans
Mice
Nuclear Proteins/genetics
RNA, Small Interfering
Repressor Proteins/genetics
Transcription, Genetic/physiology
Transplantation, Heterologous
Tumor Protein p73
Tumor Suppressor Protein p53/genetics
Tumor Suppressor Proteins/genetics

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10.1016/j.ccr.2010.05.027

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Bruno, T., Desantis, A., Bossi, G., Di Agostino, S., Sorino, C., De Nicola, F., Iezzi, S., Franchitto, A., Benassi, B., Galanti, S., La Rosa, F., Floridi, A., Bellacosa, A., Passananti, C., Blandino, G., & Fanciulli, M. (2010). Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation. Cancer Cell, 18(2), 122-134. https://doi.org/10.1016/j.ccr.2010.05.027

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title = "Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation",

abstract = "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.",

keywords = "Animals, Apoptosis, Apoptosis Regulatory Proteins/genetics, Breast Neoplasms/genetics, Cell Line, Tumor, Cell Survival/physiology, DNA Damage, DNA Repair/physiology, DNA-Binding Proteins/genetics, Humans, Mice, Nuclear Proteins/genetics, RNA, Small Interfering, Repressor Proteins/genetics, Transcription, Genetic/physiology, Transplantation, Heterologous, Tumor Protein p73, Tumor Suppressor Protein p53/genetics, Tumor Suppressor Proteins/genetics",

author = "Tiziana Bruno and Agata Desantis and Gianluca Bossi and {Di Agostino}, Silvia and Cristina Sorino and {De Nicola}, Francesca and Simona Iezzi and Annapaola Franchitto and Barbara Benassi and Sergio Galanti and {La Rosa}, Francesca and Aristide Floridi and Alfonso Bellacosa and Claudio Passananti and Giovanni Blandino and Maurizio Fanciulli",

year = "2010",

month = aug,

doi = "10.1016/j.ccr.2010.05.027",

language = "English",

volume = "18",

pages = "122--134",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "2",

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Bruno, T, Desantis, A, Bossi, G, Di Agostino, S, Sorino, C, De Nicola, F, Iezzi, S, Franchitto, A, Benassi, B, Galanti, S, La Rosa, F, Floridi, A, Bellacosa, A, Passananti, C, Blandino, G & Fanciulli, M 2010, 'Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation', Cancer Cell, vol. 18, no. 2, pp. 122-134. https://doi.org/10.1016/j.ccr.2010.05.027

TY - JOUR

T1 - Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation

AU - Bruno, Tiziana

AU - Desantis, Agata

AU - Bossi, Gianluca

AU - Di Agostino, Silvia

AU - Sorino, Cristina

AU - De Nicola, Francesca

AU - Iezzi, Simona

AU - Franchitto, Annapaola

AU - Benassi, Barbara

AU - Galanti, Sergio

AU - La Rosa, Francesca

AU - Floridi, Aristide

AU - Bellacosa, Alfonso

AU - Passananti, Claudio

AU - Blandino, Giovanni

AU - Fanciulli, Maurizio

PY - 2010/8

Y1 - 2010/8

N2 - 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.

AB - 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.

KW - Animals

KW - Apoptosis

KW - Apoptosis Regulatory Proteins/genetics

KW - Breast Neoplasms/genetics

KW - Cell Line, Tumor

KW - Cell Survival/physiology

KW - DNA Damage

KW - DNA Repair/physiology

KW - DNA-Binding Proteins/genetics

KW - Humans

KW - Mice

KW - Nuclear Proteins/genetics

KW - RNA, Small Interfering

KW - Repressor Proteins/genetics

KW - Transcription, Genetic/physiology

KW - Transplantation, Heterologous

KW - Tumor Protein p73

KW - Tumor Suppressor Protein p53/genetics

KW - Tumor Suppressor Proteins/genetics

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U2 - 10.1016/j.ccr.2010.05.027

DO - 10.1016/j.ccr.2010.05.027

M3 - Article

C2 - 20708154

SN - 1535-6108

VL - 18

SP - 122

EP - 134

JO - Cancer Cell

JF - Cancer Cell

IS - 2

ER -

Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation

Abstract

Keywords

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