SâGlutathionylation and SâNitrosylation as Modulators of Redox-Dependent Processes in Cancer Cell

• Published in: Biochemistry (Moscow) 2023-07, Vol.88 (7), p.924
• Main Authors: Kalinina, Elena V, Novichkova, Maria D
• Format: Article
• Language: English
• Subjects: Analysis; Cancer cells; Chemical processes; Methods; Oxidation-reduction reaction
• ISSN: 0006-2979
• DOI: 10.1134/S0006297923070064

Development of oxidative/nitrosative stress associated with the activation of oncogenic pathways results from the increase in the generation of reactive oxygen and nitrogen species (ROS/RNS) in tumor cells, where they can have a dual effect. At high concentrations, ROS/RNS cause cell death and limit tumor growth at certain phases of its development, while their low amounts promote oxidative/nitrosative modifications of key redox-dependent residues in regulatory proteins. The reversibility of such modifications as Sâglutathionylation and Sânitrosylation that proceed through the electrophilic attack of ROS/RNS on nucleophilic Cys residues ensures the redox-dependent switch in the activity of signaling proteins, as well as the ability of these compounds to control cell proliferation and programmed cell death. The content of Sâglutathionylated and Sânitrosylated proteins is controlled by the balance between Sâglutathionylation/deglutathionylation and Sânitrosylation/denitrosylation, respectively, and depends on the cellular redox status. The extent of Sâglutathionylation and Sânitrosylation of protein targets and their ratio largely determine the status and direction of signaling pathways in cancer cells. The review discusses the features of Sâglutathionylation and Sânitrosylation reactions and systems that control them in cancer cells, as well as their relationship with redox-dependent processes and tumor growth.