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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
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
_version_	1718423862038757376

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

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