P300 cooperates with c-Jun and PARP-1 at the p300 binding site to activate RhoB transcription in NSC126188-mediated apoptosis

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Title
P300 cooperates with c-Jun and PARP-1 at the p300 binding site to activate RhoB transcription in NSC126188-mediated apoptosis
Author(s)
Bo Kyung KimJoo-Young Im; G Han; W J Lee; Kyoung Jae Won; Kyung-Sook Chung; K Lee; Hyun Seung Ban; K B Song; Mi Sun Won
Bibliographic Citation
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms, vol. 1839, no. 5, pp. 364-373
Publication Year
2014
Abstract
The anti-cancer agent NSC126188 induces apoptosis of stomach carcinoma NUGC-3 cells by inducing RhoB expression. Here, we present that the p300 binding site in the RhoB promoter is crucial for the binding of p300 and its partner transcription factors to activate RhoB transcription in NSC126188-mediated apoptosis. NSC126188 increased expression of p300 and c-Jun. Conversely, knockdown of p300 decreased RhoB expression in the presence of NSC126188. We found that poly(ADP-ribose) polymerase-1 (PARP-1) was associated with the p300 binding site and that PARP-1 knockdown inhibited NSC126188-mediated RhoB expression. In the cells treated with NSC126188, p300, PARP-1, and c-Jun interacted and bound the p300 binding site. Furthermore, chromatin immunoprecipitation (ChIP) analysis revealed strong p300 binding and weak c-Jun binding at the p300 binding site of RhoB promoter in cells treated with NSC126188. We also demonstrated that c-Jun played a crucial role in p300 binding. However, PARP-1 did not directly bind the p300 binding site, suggesting a bridging role between p300 and c-Jun. Electrophoretic mobility shift assays demonstrated a complex comprising p300/c-Jun/PARP-1 that bound wild type, but not a mutated, p300 binding site. In addition, overexpression of p300, PARP-1, or c-Jun dramatically enhanced RhoB promoter activity when it contained the wild type sequence but not mutated sequences, indicating the crucial role of the p300 binding site in NSC126188-induced transcription of RhoB. Taken together, these data suggest that p300 is recruited and cooperates with c-Jun and PARP-1 at the p300 binding site to activate RhoB transcription during NSC126188-mediated apoptosis.
Keyword
ApoptosisC-JunNSC126188P300PARP-1RhoB
ISSN
1874-9399
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bbagrm.2014.03.004
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Research on National Challenges > 1. Journal Articles
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
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