Increased migration and motility in XIAP-null cells mediated by the C-RAF protein kinase

Russell, Lauren G, Davis, Lydia AK, Hunter, Jill E, Perkins, Neil D and Kenneth, Niall S ORCID: 0000-0001-8528-1021 (2021) Increased migration and motility in XIAP-null cells mediated by the C-RAF protein kinase. [Preprint]

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Official URL: http://dx.doi.org/10.21203/rs.3.rs-923703/v1

Abstract

<jats:title>Abstract</jats:title> <jats:p>The product encoded by the X-linked inhibitor of apoptosis (XIAP) gene is a multi-functional protein which not only controls caspase-dependent cell death, but also participates in inflammatory signalling, copper homeostasis, response to hypoxia and control of cell migration. Deregulation of XIAP, either by elevated expression or inherited genetic deletion, is associated with several human disease states. Reconciling XIAP-dependent signalling pathways with its role in disease progression is essential to understand how XIAP promotes the progression of human pathologies. In this study we have created a panel of genetically modified XIAP-null cell lines using TALENs and CRISPR/Cas9 to investigate the functional outcome of XIAP deletion. Surprisingly, in our genetically modified cells XIAP deletion had no effect on programmed cell death, but instead the primary phenotype we observed was a profound increase in cell migration rates. Furthermore, we found that XIAP-dependent suppression of cell migration was dependent on XIAP-dependent control of C-RAF levels, a protein kinase which controls cell signalling pathways that regulate the cytoskeleton. These results suggest that XIAP is not necessary for control of the apoptotic signalling cascade, however it does have a critical role in controlling cell migration and motility that cannot be compensated for in XIAP-knockout cells.</jats:p>

Item Type:	Preprint
Uncontrolled Keywords:	Genetics, 2 Aetiology, 2.1 Biological and endogenous factors, 1 Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	05 Oct 2021 10:45
Last Modified:	12 Apr 2024 13:29
DOI:	10.21203/rs.3.rs-923703/v1
Related URLs:	Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3139365