TAp73-mediated the activation of c-Jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells.

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 gene...

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Autores principales: Pingde Zhang, Stephanie Si Liu, Hextan Yuen Sheung Ngan
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/8632a0fcc81c41eea1738630394de85f
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spelling oai:doaj.org-article:8632a0fcc81c41eea1738630394de85f2021-11-18T07:09:04ZTAp73-mediated the activation of c-Jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells.1932-620310.1371/journal.pone.0042985https://doaj.org/article/8632a0fcc81c41eea1738630394de85f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22900074/?tool=EBIhttps://doaj.org/toc/1932-6203P73, 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 (GADD45α) 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 GADD45α 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.Pingde ZhangStephanie Si LiuHextan Yuen Sheung NganPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e42985 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Pingde Zhang
Stephanie Si Liu
Hextan Yuen Sheung Ngan
TAp73-mediated the activation of c-Jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells.
description 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 (GADD45α) 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 GADD45α 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.
format article
author Pingde Zhang
Stephanie Si Liu
Hextan Yuen Sheung Ngan
author_facet Pingde Zhang
Stephanie Si Liu
Hextan Yuen Sheung Ngan
author_sort Pingde Zhang
title TAp73-mediated the activation of c-Jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells.
title_short TAp73-mediated the activation of c-Jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells.
title_full TAp73-mediated the activation of c-Jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells.
title_fullStr TAp73-mediated the activation of c-Jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells.
title_full_unstemmed TAp73-mediated the activation of c-Jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells.
title_sort tap73-mediated the activation of c-jun n-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/8632a0fcc81c41eea1738630394de85f
work_keys_str_mv AT pingdezhang tap73mediatedtheactivationofcjunnterminalkinaseenhancescellularchemosensitivitytocisplatininovariancancercells
AT stephaniesiliu tap73mediatedtheactivationofcjunnterminalkinaseenhancescellularchemosensitivitytocisplatininovariancancercells
AT hextanyuensheungngan tap73mediatedtheactivationofcjunnterminalkinaseenhancescellularchemosensitivitytocisplatininovariancancercells
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