scholarly journals Transcriptional Repression of the Anti-apoptoticsurvivinGene by Wild Type p53

2001 ◽  
Vol 277 (5) ◽  
pp. 3247-3257 ◽  
Author(s):  
William H. Hoffman ◽  
Siham Biade ◽  
Jack T. Zilfou ◽  
Jiandong Chen ◽  
Maureen Murphy
Keyword(s):  
Transcriptional Repression ◽  
Wild Type ◽  
Wild Type P53

scholarly journals Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a

1999 ◽  
Vol 13 (19) ◽  
pp. 2490-2501 ◽  
Author(s):  
M. Murphy ◽  
J. Ahn ◽  
K. K. Walker ◽  
W. H. Hoffman ◽  
R. M. Evans ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Histone Deacetylases ◽  
Wild Type ◽  
Wild Type P53

scholarly journals Transcriptional repression ofAurora-Agene by wild-type p53 through directly binding to its promoter with histone deacetylase 1 and mSin3a

2017 ◽  
Vol 142 (1) ◽  
pp. 92-108
Author(s):  
Tsung-Ying Yang ◽  
Chieh-Lin Jerry Teng ◽  
Tsung-Chieh Chester Lin ◽  
Kun-Chieh Chen ◽  
Shih-Lan Hsu ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Wild Type ◽  
Histone Deacetylase 1 ◽  
Wild Type P53

scholarly journals An MDM2 inhibitor achieves synergistic cytotoxic effects with adenoviruses lacking E1B55kDa gene on mesothelioma with the wild-type p53 through augmenting NFI expression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Thao Thi Thanh Nguyen ◽  
Masato Shingyoji ◽  
Michiko Hanazono ◽  
Boya Zhong ◽  
Takao Morinaga ◽  
...  
Keyword(s):  
Wild Type ◽  
Inhibitory Effects ◽  
Cytotoxic Effects ◽  
P53 Expression ◽  
Nuclear Factor I ◽  
Infected Cells ◽  
Wild Type P53 ◽  
Mdm2 Inhibitor ◽  
P16 Expression

AbstractA majority of mesothelioma specimens were defective of p14 and p16 expression due to deletion of the INK4A/ARF region, and the p53 pathway was consequently inactivated by elevated MDM2 functions which facilitated p53 degradaton. We investigated a role of p53 elevation by MDM2 inhibitors, nutlin-3a and RG7112, in cytotoxicity of replication-competent adenoviruses (Ad) lacking the p53-binding E1B55kDa gene (Ad-delE1B). We found that a growth inhibition by p53-activating Ad-delE1B was irrelevant to p53 expression in the infected cells, but combination of Ad-delE1B and the MDM2 inhibitor produced synergistic inhibitory effects on mesothelioma with the wild-type but not mutated p53 genotype. The combination augmented p53 phosphorylation, activated apoptotic but not autophagic pathway, and enhanced DNA damage signals through ATM-Chk2 phosphorylation. The MDM2 inhibitors facilitated production of the Ad progenies through augmented expression of nuclear factor I (NFI), one of the transcriptional factors involved in Ad replications. Knocking down of p53 with siRNA did not increase the progeny production or the NFI expression. We also demonstrated anti-tumor effects by the combination of Ad-delE1B and the MDM2 inhibitors in an orthotopic animal model. These data collectively indicated that upregulation of wild-type p53 expression contributed to cytotoxicity by E1B55kDa-defective replicative Ad through NFI induction and suggested that replication-competent Ad together with augmented p53 levels was a therapeutic strategy for p53 wild-type mesothelioma.

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