Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation.
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.
Bruno
Tiziana
T
Department of Therapeutic Programs Development, Regina Elena Cancer Institute, Rome, Italy.
Desantis
Agata
A
Bossi
Gianluca
G
Di Agostino
Silvia
S
Sorino
Cristina
C
De Nicola
Francesca
F
Iezzi
Simona
S
Franchitto
Annapaola
A
Benassi
Barbara
B
Galanti
Sergio
S
La Rosa
Francesca
F
Floridi
Aristide
A
Bellacosa
Alfonso
A
Passananti
Claudio
C
Blandino
Giovanni
G
Fanciulli
Maurizio
M
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014183:Transplantation, Heterologous; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics
C402637:AATF protein, human; D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins