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

IRCCS Istituti fisioterapici ospitalieri - Istituto Regina Elena
University of L'Aquila
Istituto Superiore di Sanita
National Research Council of Italy

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

42 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

@article{e4b15b3663614dd78610885f273809ee,

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

UR - https://www.scopus.com/pages/publications/77955522727

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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