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Article: TAp73-mediated the activation of C-jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells
Title | TAp73-mediated the activation of C-jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells |
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Authors | |
Keywords | Cisplatin Growth arrest and DNA damage inducible protein 45 Growth arrest and DNA damage inducible protein 45 alpha Mitogen activated protein kinase kinase 4 Protein p73 |
Issue Date | 2012 |
Publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action |
Citation | PLoS One, 2012, v. 7 n. 8, article no. e42985 How to Cite? |
Abstract | P73, one member of the tumor suppressor p53 family, shares highly structural and functional similarity to p53. Like p53, the transcriptionally active TAp73 can mediate cellular response to chemotherapeutic agents in human cancer cells by up-regulating the expressions of its pro-apoptotic target genes such as PUMA, Bax, NOXA. Here, we demonstrated a novel molecular mechanism for TAp73-mediated apoptosis in response to cisplatin in ovarian cancer cells, and that was irrespective of p53 status. We found that TAp73 acted as an activator of the c-Jun N-terminal kinase (JNK) signaling pathway by up-regulating the expression of its target growth arrest and DNA-damage-inducible protein GADD45 alpha (GADD45alpha) and subsequently activating mitogen-activated protein kinase kinase-4 (MKK4). Inhibition of JNK activity by a specific inhibitor or small interfering RNA (siRNA) significantly abrogated TAp73-mediated apoptosis induced by cisplatin. Furthermore, inhibition of GADD45alpha by siRNA inactivated MKK4/JNK activities and also blocked TAp73-mediated apoptosis induction by cisplatin. Our study has demonstrated that TAp73 activated the JNK apoptotic signaling pathway in response to cisplatin in ovarian cancer cells. |
Persistent Identifier | http://hdl.handle.net/10722/173380 |
ISSN | 2023 Impact Factor: 2.9 2023 SCImago Journal Rankings: 0.839 |
PubMed Central ID | |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
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dc.contributor.author | Zhang, P | en_US |
dc.contributor.author | Liu, SS | en_US |
dc.contributor.author | Ngan, HYS | en_US |
dc.date.accessioned | 2012-10-30T06:29:57Z | - |
dc.date.available | 2012-10-30T06:29:57Z | - |
dc.date.issued | 2012 | en_US |
dc.identifier.citation | PLoS One, 2012, v. 7 n. 8, article no. e42985 | en_US |
dc.identifier.issn | 1932-6203 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/173380 | - |
dc.description.abstract | P73, one member of the tumor suppressor p53 family, shares highly structural and functional similarity to p53. Like p53, the transcriptionally active TAp73 can mediate cellular response to chemotherapeutic agents in human cancer cells by up-regulating the expressions of its pro-apoptotic target genes such as PUMA, Bax, NOXA. Here, we demonstrated a novel molecular mechanism for TAp73-mediated apoptosis in response to cisplatin in ovarian cancer cells, and that was irrespective of p53 status. We found that TAp73 acted as an activator of the c-Jun N-terminal kinase (JNK) signaling pathway by up-regulating the expression of its target growth arrest and DNA-damage-inducible protein GADD45 alpha (GADD45alpha) and subsequently activating mitogen-activated protein kinase kinase-4 (MKK4). Inhibition of JNK activity by a specific inhibitor or small interfering RNA (siRNA) significantly abrogated TAp73-mediated apoptosis induced by cisplatin. Furthermore, inhibition of GADD45alpha by siRNA inactivated MKK4/JNK activities and also blocked TAp73-mediated apoptosis induction by cisplatin. Our study has demonstrated that TAp73 activated the JNK apoptotic signaling pathway in response to cisplatin in ovarian cancer cells. | en_US |
dc.language | eng | en_US |
dc.publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action | en_US |
dc.relation.ispartof | PLoS ONE | en_US |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Cisplatin | - |
dc.subject | Growth arrest and DNA damage inducible protein 45 | - |
dc.subject | Growth arrest and DNA damage inducible protein 45 alpha | - |
dc.subject | Mitogen activated protein kinase kinase 4 | - |
dc.subject | Protein p73 | - |
dc.title | TAp73-mediated the activation of C-jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells | en_US |
dc.type | Article | en_US |
dc.identifier.email | Liu, SS: stephasl@hku.hk | en_US |
dc.identifier.email | Ngan, HYS: hysngan@hkucc.hku.hk | en_US |
dc.identifier.authority | Liu, SS=rp00372 | en_US |
dc.identifier.authority | Ngan, HYS=rp00346 | en_US |
dc.description.nature | published_or_final_version | en_US |
dc.identifier.doi | 10.1371/journal.pone.0042985 | en_US |
dc.identifier.pmid | 22900074 | - |
dc.identifier.pmcid | PMC3416758 | - |
dc.identifier.scopus | eid_2-s2.0-84864964240 | en_US |
dc.identifier.hkuros | 207764 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-84864964240&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 7 | en_US |
dc.identifier.issue | 8, article no. e42985 | en_US |
dc.identifier.isi | WOS:000307380900092 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Ngan, HYS=34571944100 | en_US |
dc.identifier.scopusauthorid | Liu, SS=37102450400 | en_US |
dc.identifier.scopusauthorid | Zhang, P=55336833100 | en_US |
dc.identifier.issnl | 1932-6203 | - |