RAS-Dependent Mitogen-Activated Protein Kinase Hyperactivation by Pathogenic RIT1
- Description
The RAS family of small guanosine triphosphatases (GTPases) control a diverse network of signaling pathways essential for human development and adult tissue homeostasis. RAS-related GTPase RIT1 proteins promote mitogen-activated protein kinase (MAPK) hyperactivation, but this mechanism remains poorly understood. This study examined whether MEK1/2 inhibition attenuates MAPK signaling in RIT1 M90I mice and ameliorates cardiac tissue overgrowth. They treated a cohort of 4-week-old mice harboring a germline Rit1M90I variant with the allosteric MEK1/2 inhibitor trametinib.
In addition, they isolated neonatal cardiomyocytes from mice harboring an engineered Rit1 locus with Cre recombinase-inducible expression of the pathogenic variant Rit1M90I to investigate the impact of mutant RIT1 expression in cardiac cells. Upon isolation, cardiomyocytes were treated with adenoviruses encoding for Cre recombinase to induce expression of the Rit1M90I variant. The dataset contains comparative gene expression profiling analysis of RNA sequencing data for heart tissue isolated from Rit1 M90I/+ mice treated with Trametinib (1mg/kg) or vehicle control for 20 weeks starting at 4 weeks of age, and comparative gene expression profiling analysis of RNA sequencing data for primary cardiomyocytes expressing WT RIT1 or RIT1 (M90I).
Access
- Restrictions
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Free to All
- Instructions
- RNA sequencing data from this publication have been deposited in Gene Expression Omnibus (GEO).
- Grant Support
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TRF Early Career Award/Thrasher Research FoundationW81XWH-20-1-0391/Congressionally Directed Medical Research ProgramsLaboratory Directed Exploratory Research Program/Frederick National Laboratory for Cancer Research