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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2012
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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) |
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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 |
_version_ |
1718423862038757376 |