Control of tissue growth and cell transformation by the Salvador/Warts/Hippo pathway.

The Salvador-Warts-Hippo (SWH) pathway is an important regulator of tissue growth that is frequently subverted in human cancer. The key oncoprotein of the SWH pathway is the transcriptional co-activator, Yes-associated protein (YAP). YAP promotes tissue growth and transformation of cultured cells by...

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Autores principales:	Xiaomeng Zhang, Felix A Grusche, Kieran F Harvey
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f1952c83599a40a59730544435d57999
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spelling	oai:doaj.org-article:f1952c83599a40a59730544435d579992021-11-18T07:27:54ZControl of tissue growth and cell transformation by the Salvador/Warts/Hippo pathway.1932-620310.1371/journal.pone.0031994https://doaj.org/article/f1952c83599a40a59730544435d579992012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22359650/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The Salvador-Warts-Hippo (SWH) pathway is an important regulator of tissue growth that is frequently subverted in human cancer. The key oncoprotein of the SWH pathway is the transcriptional co-activator, Yes-associated protein (YAP). YAP promotes tissue growth and transformation of cultured cells by interacting with transcriptional regulatory proteins via its WW domains, or, in the case of the TEAD1-4 transcription factors, an N-terminal binding domain. YAP possesses a putative transactivation domain in its C-terminus that is necessary to stimulate transcription factors in vitro, but its requirement for YAP function has not been investigated in detail. Interestingly, whilst the WW domains and TEAD-binding domain are highly conserved in the Drosophila melanogaster YAP orthologue, Yorkie, the majority of the C-terminal region of YAP is not present in Yorkie. To investigate this apparent conundrum, we assessed the functional roles of the YAP and Yorkie C-termini. We found that these regions were not required for Yorkie's ability to drive tissue growth in vivo, or YAP's ability to promote anchorage-independent growth or resistance to contact inhibition. However, the YAP transactivation domain was required for YAP's ability to induce cell migration and invasion. Moreover, a role for the YAP transactivation domain in cell transformation was uncovered when the YAP WW domains were mutated together with the transactivation domain. This shows that YAP can promote cell transformation in a flexible manner, presumably by contacting transcriptional regulatory proteins either via its WW domains or its transactivation domain.Xiaomeng ZhangFelix A GruscheKieran F HarveyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31994 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaomeng Zhang Felix A Grusche Kieran F Harvey Control of tissue growth and cell transformation by the Salvador/Warts/Hippo pathway.
description	The Salvador-Warts-Hippo (SWH) pathway is an important regulator of tissue growth that is frequently subverted in human cancer. The key oncoprotein of the SWH pathway is the transcriptional co-activator, Yes-associated protein (YAP). YAP promotes tissue growth and transformation of cultured cells by interacting with transcriptional regulatory proteins via its WW domains, or, in the case of the TEAD1-4 transcription factors, an N-terminal binding domain. YAP possesses a putative transactivation domain in its C-terminus that is necessary to stimulate transcription factors in vitro, but its requirement for YAP function has not been investigated in detail. Interestingly, whilst the WW domains and TEAD-binding domain are highly conserved in the Drosophila melanogaster YAP orthologue, Yorkie, the majority of the C-terminal region of YAP is not present in Yorkie. To investigate this apparent conundrum, we assessed the functional roles of the YAP and Yorkie C-termini. We found that these regions were not required for Yorkie's ability to drive tissue growth in vivo, or YAP's ability to promote anchorage-independent growth or resistance to contact inhibition. However, the YAP transactivation domain was required for YAP's ability to induce cell migration and invasion. Moreover, a role for the YAP transactivation domain in cell transformation was uncovered when the YAP WW domains were mutated together with the transactivation domain. This shows that YAP can promote cell transformation in a flexible manner, presumably by contacting transcriptional regulatory proteins either via its WW domains or its transactivation domain.
format	article
author	Xiaomeng Zhang Felix A Grusche Kieran F Harvey
author_facet	Xiaomeng Zhang Felix A Grusche Kieran F Harvey
author_sort	Xiaomeng Zhang
title	Control of tissue growth and cell transformation by the Salvador/Warts/Hippo pathway.
title_short	Control of tissue growth and cell transformation by the Salvador/Warts/Hippo pathway.
title_full	Control of tissue growth and cell transformation by the Salvador/Warts/Hippo pathway.
title_fullStr	Control of tissue growth and cell transformation by the Salvador/Warts/Hippo pathway.
title_full_unstemmed	Control of tissue growth and cell transformation by the Salvador/Warts/Hippo pathway.
title_sort	control of tissue growth and cell transformation by the salvador/warts/hippo pathway.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/f1952c83599a40a59730544435d57999
work_keys_str_mv	AT xiaomengzhang controloftissuegrowthandcelltransformationbythesalvadorwartshippopathway AT felixagrusche controloftissuegrowthandcelltransformationbythesalvadorwartshippopathway AT kieranfharvey controloftissuegrowthandcelltransformationbythesalvadorwartshippopathway
_version_	1718423447056416768

Control of tissue growth and cell transformation by the Salvador/Warts/Hippo pathway.

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