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

Bo Kyung Kim, Joo Young Im, Gyoonhee Han, Woo Jung Lee, Kyoung Jae Won, Kyung Sook Chung, Kyeong Lee, Hyun Seung Ban, Kyung Bin Song, Misun Won

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)364-373
Number of pages10
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1839
Issue number5
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

4-hexadecanoyl-1,1-dimethylpiperazin-1-ium
Poly(ADP-ribose) Polymerases
Transcription
Binding Sites
Apoptosis
Electrophoretic mobility
Poly (ADP-Ribose) Polymerase-1
Chromatin Immunoprecipitation
Electrophoretic Mobility Shift Assay

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Kim, Bo Kyung ; Im, Joo Young ; Han, Gyoonhee ; Lee, Woo Jung ; Won, Kyoung Jae ; Chung, Kyung Sook ; Lee, Kyeong ; Ban, Hyun Seung ; Song, Kyung Bin ; Won, Misun. / P300 cooperates with c-Jun and PARP-1 at the p300 binding site to activate RhoB transcription in NSC126188-mediated apoptosis. In: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms. 2014 ; Vol. 1839, No. 5. pp. 364-373.
@article{3432ee5581084fa1a0e73c6e2ff9fab3,
title = "P300 cooperates with c-Jun and PARP-1 at the p300 binding site to activate RhoB transcription in NSC126188-mediated apoptosis",
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.",
author = "Kim, {Bo Kyung} and Im, {Joo Young} and Gyoonhee Han and Lee, {Woo Jung} and Won, {Kyoung Jae} and Chung, {Kyung Sook} and Kyeong Lee and Ban, {Hyun Seung} and Song, {Kyung Bin} and Misun Won",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.bbagrm.2014.03.004",
language = "English",
volume = "1839",
pages = "364--373",
journal = "Biochimica et Biophysica Acta - Gene Regulatory Mechanisms",
issn = "1874-9399",
publisher = "Elsevier",
number = "5",

}

P300 cooperates with c-Jun and PARP-1 at the p300 binding site to activate RhoB transcription in NSC126188-mediated apoptosis. / Kim, Bo Kyung; Im, Joo Young; Han, Gyoonhee; Lee, Woo Jung; Won, Kyoung Jae; Chung, Kyung Sook; Lee, Kyeong; Ban, Hyun Seung; Song, Kyung Bin; Won, Misun.

In: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, Vol. 1839, No. 5, 01.01.2014, p. 364-373.

Research output: Contribution to journalArticle

TY - JOUR

T1 - P300 cooperates with c-Jun and PARP-1 at the p300 binding site to activate RhoB transcription in NSC126188-mediated apoptosis

AU - Kim, Bo Kyung

AU - Im, Joo Young

AU - Han, Gyoonhee

AU - Lee, Woo Jung

AU - Won, Kyoung Jae

AU - Chung, Kyung Sook

AU - Lee, Kyeong

AU - Ban, Hyun Seung

AU - Song, Kyung Bin

AU - Won, Misun

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84897372498&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897372498&partnerID=8YFLogxK

U2 - 10.1016/j.bbagrm.2014.03.004

DO - 10.1016/j.bbagrm.2014.03.004

M3 - Article

C2 - 24636898

AN - SCOPUS:84897372498

VL - 1839

SP - 364

EP - 373

JO - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms

JF - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms

SN - 1874-9399

IS - 5

ER -