Cysteine-based regulation of redox-sensitive Ras small GTPases.

Animals Cell Transformation, Neoplastic Cysteine / metabolism Gene Expression Regulation Humans Oxidation-Reduction Protein Isoforms Protein Processing, Post-Translational Reactive Nitrogen Species / metabolism Reactive Oxygen Species / metabolism Signal Transduction Structure-Activity Relationship ras Proteins / chemistry
Cysteine 118 Ras small GTPases Redox-signalling

Journal

Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639

Informations de publication

Date de publication:
09 2019
Historique:
received: 03 06 2019
revised: 21 07 2019
accepted: 24 07 2019
pubmed: 7 8 2019
medline: 28 2 2020
entrez: 7 8 2019
Statut: ppublish

Résumé

Reactive oxygen and nitrogen species (ROS and RNS, respectively) activate the redox-sensitive Ras small GTPases. The three canonical genes (HRAS, NRAS, and KRAS) are archetypes of the superfamily of small GTPases and are the most common oncogenes in human cancer. Oncogenic Ras is intimately linked to redox biology, mainly in the context of tumorigenesis. The Ras protein structure is highly conserved, especially in effector-binding regions. Ras small GTPases are redox-sensitive proteins thanks to the presence of the NKCD motif (Asn116-Lys 117-Cys118-Asp119). Notably, the ROS- and RNS-based oxidation of Cys118 affects protein stability, activity, and localization, and protein-protein interactions. Cys residues at positions 80, 181, 184, and 186 may also help modulate these actions. Moreover, oncogenic mutations of Gly12Cys and Gly13Cys may introduce additional oxidative centres and represent actionable drug targets. Here, the pathophysiological involvement of Cys-redox regulation of Ras proteins is reviewed in the context of cancer and heart and brain diseases.

Identifiants

DOI: 10.1016/j.redox.2019.101282 PMID: 31386964 PMC: PMC6695279
pubmed: 31386964
pii: S2213-2317(19)30642-1
doi: 10.1016/j.redox.2019.101282
pmc: PMC6695279
pii:
doi:

Substances chimiques

Protein Isoforms 0
Reactive Nitrogen Species 0
Reactive Oxygen Species 0
ras Proteins EC 3.6.5.2
Cysteine K848JZ4886

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

101282

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

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Auteurs

Samantha Messina (S)

Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, I-00146, Roma, Italy. Electronic address: samantha.messina@uniroma1.it.

Giovanna De Simone (G)

Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, I-00146, Roma, Italy.

Paolo Ascenzi (P)

Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, I-00146, Roma, Italy.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Cysteine-based regulation of redox-sensitive...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Carcinogenèse › Transformation cellulaire néoplasique › Cysteine-based regulation of redox-sensitive...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés soufrés › Cystéine › Cysteine-based regulation of redox-sensitive...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Cysteine-based regulation of redox-sensitive...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Cysteine-based regulation of redox-sensitive...
questionsmedicales.fr › Métabolisme › Métabolisme énergétique › Oxydoréduction › Cysteine-based regulation of redox-sensitive...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Isoformes de protéines › Cysteine-based regulation of redox-sensitive...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Modification traductionnelle des protéines › Maturation post-traductionnelle des protéines › Cysteine-based regulation of redox-sensitive...
questionsmedicales.fr › Composés chimiques organiques › Composés nitrosés › Espèces réactives de l'azote › Cysteine-based regulation of redox-sensitive...
questionsmedicales.fr › Produits chimiques inorganiques › Composés de l'oxygène › Espèces réactives de l'oxygène › Cysteine-based regulation of redox-sensitive...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Cysteine-based regulation of redox-sensitive...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › Cysteine-based regulation of redox-sensitive...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines G › Protéines G monomériques › Protéines G ras › Cysteine-based regulation of redox-sensitive...