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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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 |
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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 |
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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. |
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School of Biological Sciences |
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School of Biological Sciences Muhammad Bakhait Rahmat Zhang, Songjing Koh, Cheng-Gee |
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Article |
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Muhammad Bakhait Rahmat Zhang, Songjing Koh, Cheng-Gee |
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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 |
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2019 |
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https://hdl.handle.net/10356/90014 http://hdl.handle.net/10220/49377 |
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