Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

IQGAP is a Scaffold of the Core Proteins of the Hippo Pathway and Negatively Regulates the Pro-Apoptotic Signal Mediated by This Pathway

Version 1 : Received: 13 February 2021 / Approved: 16 February 2021 / Online: 16 February 2021 (14:08:12 CET)

A peer-reviewed article of this Preprint also exists.

Quinn, N.P.; García-Gutiérrez, L.; Doherty, C.; von Kriegsheim, A.; Fallahi, E.; Sacks, D.B.; Matallanas, D. IQGAP1 Is a Scaffold of the Core Proteins of the Hippo Pathway and Negatively Regulates the Pro-Apoptotic Signal Mediated by this Pathway. Cells 2021, 10, 478. Quinn, N.P.; García-Gutiérrez, L.; Doherty, C.; von Kriegsheim, A.; Fallahi, E.; Sacks, D.B.; Matallanas, D. IQGAP1 Is a Scaffold of the Core Proteins of the Hippo Pathway and Negatively Regulates the Pro-Apoptotic Signal Mediated by this Pathway. Cells 2021, 10, 478.

Journal reference: Cells 2021, 10, 478
DOI: 10.3390/cells10020478

Abstract

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.

Keywords

IQGAP1; MST2; LATS1, YAP1, Hippo, Bile acid, hepatocellular carcinoma.

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