IQGAP1 Is a Scaffold of the Core Proteins of the Hippo Pathway and Negatively Regulates the Pro-Apoptotic Signal Mediated by This Pathway
The Hippo pathway regulates a complex signalling network which mediates several biological functions including cell proliferation, organ size and apoptosis. Several scaffold proteins regulate the crosstalk of the members of the pathway with other signalling pathways and play an important role in the...
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MDPI AG
2021-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/2/478 |
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| author | Niall P. Quinn Lucía García-Gutiérrez Carolanne Doherty Alexander von Kriegsheim Emma Fallahi David B. Sacks David Matallanas |
| author_facet | Niall P. Quinn Lucía García-Gutiérrez Carolanne Doherty Alexander von Kriegsheim Emma Fallahi David B. Sacks David Matallanas |
| author_sort | Niall P. Quinn |
| collection | DOAJ |
| description | The Hippo pathway regulates a complex signalling network which mediates several biological functions including cell proliferation, organ size and apoptosis. Several scaffold proteins regulate the crosstalk of the members of the pathway with other signalling pathways and play an important role in the diverse output controlled by this pathway. In this study we have identified the scaffold protein IQGAP1 as a novel interactor of the core kinases of the Hippo pathway, MST2 and LATS1. Our results indicate that IQGAP1 scaffolds MST2 and LATS1 supresses their kinase activity and YAP1-dependent transcription. Additionally, we show that IQGAP1 is a negative regulator of the non-canonical pro-apoptotic pathway and may enable the crosstalk between this pathway and the ERK and AKT signalling modules. Our data also show that bile acids regulate the IQGAP1-MST2-LATS1 signalling module in hepatocellular carcinoma cells, which could be necessary for the inhibition of MST2-dependent apoptosis and hepatocyte transformation. |
| first_indexed | 2024-03-09T00:36:07Z |
| format | Article |
| id | doaj.art-065d6c56a6254d22acdb39ebe757a709 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T00:36:07Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-065d6c56a6254d22acdb39ebe757a7092023-12-11T18:07:38ZengMDPI AGCells2073-44092021-02-0110247810.3390/cells10020478IQGAP1 Is a Scaffold of the Core Proteins of the Hippo Pathway and Negatively Regulates the Pro-Apoptotic Signal Mediated by This PathwayNiall P. Quinn0Lucía García-Gutiérrez1Carolanne Doherty2Alexander von Kriegsheim3Emma Fallahi4David B. Sacks5David Matallanas6Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, IrelandSystems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, IrelandSystems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, IrelandCancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XR, UKSystems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, IrelandDepartment of Laboratory Medicine, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USASystems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, IrelandThe Hippo pathway regulates a complex signalling network which mediates several biological functions including cell proliferation, organ size and apoptosis. Several scaffold proteins regulate the crosstalk of the members of the pathway with other signalling pathways and play an important role in the diverse output controlled by this pathway. In this study we have identified the scaffold protein IQGAP1 as a novel interactor of the core kinases of the Hippo pathway, MST2 and LATS1. Our results indicate that IQGAP1 scaffolds MST2 and LATS1 supresses their kinase activity and YAP1-dependent transcription. Additionally, we show that IQGAP1 is a negative regulator of the non-canonical pro-apoptotic pathway and may enable the crosstalk between this pathway and the ERK and AKT signalling modules. Our data also show that bile acids regulate the IQGAP1-MST2-LATS1 signalling module in hepatocellular carcinoma cells, which could be necessary for the inhibition of MST2-dependent apoptosis and hepatocyte transformation.https://www.mdpi.com/2073-4409/10/2/478IQGAP1MST2LATS1YAP1Hippobile acid |
| spellingShingle | Niall P. Quinn Lucía García-Gutiérrez Carolanne Doherty Alexander von Kriegsheim Emma Fallahi David B. Sacks David Matallanas IQGAP1 Is a Scaffold of the Core Proteins of the Hippo Pathway and Negatively Regulates the Pro-Apoptotic Signal Mediated by This Pathway Cells IQGAP1 MST2 LATS1 YAP1 Hippo bile acid |
| title | IQGAP1 Is a Scaffold of the Core Proteins of the Hippo Pathway and Negatively Regulates the Pro-Apoptotic Signal Mediated by This Pathway |
| title_full | IQGAP1 Is a Scaffold of the Core Proteins of the Hippo Pathway and Negatively Regulates the Pro-Apoptotic Signal Mediated by This Pathway |
| title_fullStr | IQGAP1 Is a Scaffold of the Core Proteins of the Hippo Pathway and Negatively Regulates the Pro-Apoptotic Signal Mediated by This Pathway |
| title_full_unstemmed | IQGAP1 Is a Scaffold of the Core Proteins of the Hippo Pathway and Negatively Regulates the Pro-Apoptotic Signal Mediated by This Pathway |
| title_short | IQGAP1 Is a Scaffold of the Core Proteins of the Hippo Pathway and Negatively Regulates the Pro-Apoptotic Signal Mediated by This Pathway |
| title_sort | iqgap1 is a scaffold of the core proteins of the hippo pathway and negatively regulates the pro apoptotic signal mediated by this pathway |
| topic | IQGAP1 MST2 LATS1 YAP1 Hippo bile acid |
| url | https://www.mdpi.com/2073-4409/10/2/478 |
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