POPX2 is a novel LATS phosphatase that regulates the Hippo pathway

The Hippo pathway regulates cell proliferation, survival, apoptosis and differentiation. During carcinogenesis, members of the Hippo pathway are mutated to avoid anoikis and promote anchorage independent growth. Although many regulators of the Hippo pathway have been reported, negative regulators of...

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Main Authors: Muhammad Bakhait Rahmat, Zhang, Songjing, Koh, Cheng-Gee
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2019
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Online Access:https://hdl.handle.net/10356/90014
http://hdl.handle.net/10220/49377
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-900142023-02-28T17:02:59Z POPX2 is a novel LATS phosphatase that regulates the Hippo pathway Muhammad Bakhait Rahmat Zhang, Songjing Koh, Cheng-Gee School of Biological Sciences Interdisciplinary Graduate School (IGS) Science::Biological sciences POPX2 Phosphatase Hippo Pathway The Hippo pathway regulates cell proliferation, survival, apoptosis and differentiation. During carcinogenesis, members of the Hippo pathway are mutated to avoid anoikis and promote anchorage independent growth. Although many regulators of the Hippo pathway have been reported, negative regulators of the hippo kinases are not well studied. Through an interactome screen, we found that POPX2 phosphatase interacts with several of the Hippo pathway core kinases, including LATS1 which is the direct kinase regulating the transcription co-activators, YAP and TAZ. Phosphorylated YAP/TAZ are retained in the cytoplasm and prevented from translocation into the nucleus to activate transcription of target genes. We found that POPX2 could dephosphorylate LATS1 on Threonine-1079, leading to inactivation of LATS1 kinase. As a result, YAP/TAZ are not phosphorylated and are able to translocate into the nucleus to activate target genes involved in cell proliferation. Furthermore, POPX2 knock-out using CRISPR in the highly metastatic MDA-MB-231 breast cancer cells results in decreased cell proliferation and impairment of anchorage independent growth. We propose that POPX2 act as a suppressor of the Hippo pathway through LATS1 dephosphorylation and inactivation. MOE (Min. of Education, S’pore) Published version 2019-07-16T07:13:19Z 2019-12-06T17:38:44Z 2019-07-16T07:13:19Z 2019-12-06T17:38:44Z 2019 Journal Article Muhammad Bakhait Rahmat., Zhang, S., & Koh, C.-G. (2019). POPX2 is a novel LATS phosphatase that regulates the Hippo pathway. Oncotarget, 10(15), 1525-1538. doi:10.18632/oncotarget.26689 https://hdl.handle.net/10356/90014 http://hdl.handle.net/10220/49377 10.18632/oncotarget.26689 en Oncotarget © 2019 Rahmat et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 14 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
POPX2 Phosphatase
Hippo Pathway
spellingShingle Science::Biological sciences
POPX2 Phosphatase
Hippo Pathway
Muhammad Bakhait Rahmat
Zhang, Songjing
Koh, Cheng-Gee
POPX2 is a novel LATS phosphatase that regulates the Hippo pathway
description The Hippo pathway regulates cell proliferation, survival, apoptosis and differentiation. During carcinogenesis, members of the Hippo pathway are mutated to avoid anoikis and promote anchorage independent growth. Although many regulators of the Hippo pathway have been reported, negative regulators of the hippo kinases are not well studied. Through an interactome screen, we found that POPX2 phosphatase interacts with several of the Hippo pathway core kinases, including LATS1 which is the direct kinase regulating the transcription co-activators, YAP and TAZ. Phosphorylated YAP/TAZ are retained in the cytoplasm and prevented from translocation into the nucleus to activate transcription of target genes. We found that POPX2 could dephosphorylate LATS1 on Threonine-1079, leading to inactivation of LATS1 kinase. As a result, YAP/TAZ are not phosphorylated and are able to translocate into the nucleus to activate target genes involved in cell proliferation. Furthermore, POPX2 knock-out using CRISPR in the highly metastatic MDA-MB-231 breast cancer cells results in decreased cell proliferation and impairment of anchorage independent growth. We propose that POPX2 act as a suppressor of the Hippo pathway through LATS1 dephosphorylation and inactivation.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Muhammad Bakhait Rahmat
Zhang, Songjing
Koh, Cheng-Gee
format Article
author Muhammad Bakhait Rahmat
Zhang, Songjing
Koh, Cheng-Gee
author_sort Muhammad Bakhait Rahmat
title POPX2 is a novel LATS phosphatase that regulates the Hippo pathway
title_short POPX2 is a novel LATS phosphatase that regulates the Hippo pathway
title_full POPX2 is a novel LATS phosphatase that regulates the Hippo pathway
title_fullStr POPX2 is a novel LATS phosphatase that regulates the Hippo pathway
title_full_unstemmed POPX2 is a novel LATS phosphatase that regulates the Hippo pathway
title_sort popx2 is a novel lats phosphatase that regulates the hippo pathway
publishDate 2019
url https://hdl.handle.net/10356/90014
http://hdl.handle.net/10220/49377
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