Detection of Ras GTPase Protein Radicals Through Immuno-spin Trapping

Overview

Journal Free Radic Biol Med

Specialties Biochemistry
Biology
General Medicine

Date 2012 Jul 24

PMID 22819983

Citations 6

Authors

Michael F Davis

Li Zhou

Marilyn Ehrenshaft

Kalina Ranguelova

Harsha P Gunawardena

Xian Chen

Marcelo G Bonini

Ronald P Mason

Sharon L Campbell

Affiliations

Soon will be listed here.

Abstract

Over the past decade immuno-spin trapping (IST) has been used to detect and identify protein radical sites in numerous heme and metalloproteins. To date, however, the technique has had little application toward nonmetalloproteins. In this study, we demonstrate the successful application of IST in a system free of transition metals and present the first conclusive evidence of (•)NO-mediated protein radical formation in the HRas GTPase. HRas is a nonmetalloprotein that plays a critical role in regulating cell-growth control. Protein radical formation in Ras GTPases has long been suspected of initiating premature release of bound guanine nucleotide. This action results in altered Ras activity both in vitro and in vivo. As described herein, successful application of IST may provide a means for detecting and identifying radical-mediated Ras activation in many different cancers and disease states in which Ras GTPases play an important role.

Citing Articles

Thiyl radicals and induction of protein degradation.

Schoneich C Free Radic Res. 2015; 50(2):143-9.

PMID: 26212409 PMC: 5118943. DOI: 10.3109/10715762.2015.1077385.

Protein thiyl radical reactions and product formation: a kinetic simulation.

Nauser T, Koppenol W, Schoneich C Free Radic Biol Med. 2014; 80:158-63.

PMID: 25499854 PMC: 5118936. DOI: 10.1016/j.freeradbiomed.2014.12.006.

Redox regulation of Rac1 by thiol oxidation.

Hobbs G, Mitchell L, Arrington M, Gunawardena H, DeCristo M, Loeser R Free Radic Biol Med. 2014; 79:237-50.

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Rho GTPases, oxidation, and cell redox control.

Hobbs G, Zhou B, Cox A, Campbell S Small GTPases. 2014; 5:e28579.

PMID: 24809833 PMC: 4114927. DOI: 10.4161/sgtp.28579.

Immuno-spin trapping from biochemistry to medicine: advances, challenges, and pitfalls. Focus on protein-centered radicals.

Gomez-Mejiba S, Zhai Z, Della-Vedova M, Munoz M, Chatterjee S, Towner R Biochim Biophys Acta. 2013; 1840(2):722-9.

PMID: 23644035 PMC: 4078024. DOI: 10.1016/j.bbagen.2013.04.039.

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