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Physical Interaction between Embryonic Stem Cell-Expressed Ras (ERas) and Arginase-1 in Quiescent Hepatic Stellate
Silke Pudewell1, Jana Lissy1, Hossein Nakhaeizadeh1
1Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
Cells
|February 15, 2022
Summary
Embryonic stem cell-expressed Ras (ERas) protein
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Embryonic stem cell-expressed Ras (ERas) is a constitutively active Ras family member.
- ERas controls critical signaling pathways, including hepatic stellate cell (HSC) maintenance.
- ERas possesses a unique N-terminal extension (Nex) with an uncharacterized function.
Purpose of the Study:
- To identify novel binding proteins of the ERas Nex.
- To investigate the functional role of ERas Nex interactions in cellular processes.
- To elucidate the role of arginase 1 (ARG1) in ERas signaling and HSC quiescence.
Main Methods:
- Affinity pull-down assays.
- Quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- Biochemical interaction and colocalization studies.
- Ex vivo HSC activation assays.
Main Results:
- Identified 76 novel binding proteins for ERas Nex peptides.
- Discovered a high-affinity interaction between ERas Nex and arginase 1 (ARG1).
- Demonstrated subcellular colocalization of ERas Nex and ARG1.
- Showed that ARG1 inhibition accelerates HSC activation ex vivo.
Conclusions:
- ERas Nex interacts with diverse cellular proteins, suggesting broad regulatory functions.
- ARG1 is a novel binding partner of ERas Nex and plays a role in maintaining HSC quiescence.
- ARG1 activity is crucial for the quiescent state of hepatic stellate cells.
