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Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry
Published on: June 7, 2018
Redox regulation of RhoA
Jongyun Heo1, Kimberly W Raines, Viorel Mocanu
1Department of Biochemistry and Biophysics, The University of North Carolina, 530 Mary Ellen Jones Building, Chapel Hill, North Carolina 27599-7260, USA.
Biochemistry
|November 30, 2006
Summary
Redox agents differentially regulate GTPases. While activating Rac1 and Cdc42, they inactivate RhoA by forming a disulfide bond, impacting cellular signaling pathways.
Area of Science:
- Biochemistry
- Cell Signaling
- Molecular Biology
Background:
- Guanine nucleotide-binding proteins (GTPases) like RhoA, Rac1, and Cdc42 are crucial for cell signaling.
- Redox agents, including superoxide and nitrogen dioxide, can modify these GTPases.
- The GXXXXGK(S/T)C motif is a known target for redox agent modification.
Purpose of the Study:
- To investigate the differential effects of redox agents on RhoA compared to Rac1 and Cdc42.
- To elucidate the molecular mechanism of RhoA inactivation by redox agents.
- To explore the impact of chemotherapeutic agents and arsenic complexes on RhoA activity.
Main Methods:
- Biochemical assays to assess guanine nucleotide binding and release.
- Analysis of protein modification through disulfide bond formation.
- Investigation of interactions between RhoA and specific chemical agents.
Main Results:
- Redox agents stimulate guanine nucleotide release from RhoA, Rac1, and Cdc42.
- RhoA undergoes inactivation via intramolecular disulfide bond formation, distinct from Rac1 and Cdc42.
- Cisplatin and arsenic complexes inactivate RhoA by forming adducts or bridging cysteine residues.
Conclusions:
- Differential redox regulation of RhoA versus Rac1/Cdc42 contributes to opposing cellular functions.
- RhoA inactivation by redox agents, cisplatin, and arsenic complexes highlights a novel regulatory mechanism.
- Targeting the RhoA GXXXCGK(S/T)C motif offers potential therapeutic strategies.
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