POPX2 is a novel LATS phosphatase that regulates the Hippo pathway
| Autor: | Cheng-Gee Koh, Songjing Zhang, Muhammad Bakhait Rahmat |
|---|---|
| Přispěvatelé: | School of Biological Sciences, Interdisciplinary Graduate School (IGS) |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Hippo pathway Phosphatase medicine.disease_cause Dephosphorylation 03 medical and health sciences 0302 clinical medicine POPX2 phosphatase medicine YAP/TAZ Anoikis Hippo signaling pathway anchorage-independent growth Kinase Cell growth Chemistry Biological sciences [Science] POPX2 Phosphatase Hippo Pathway Cell biology 030104 developmental biology LATS1 kinase Oncology 030220 oncology & carcinogenesis Phosphorylation Carcinogenesis Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.26689 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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