REVIEW: S-Glutathionylation and S-Nitrosylation as Modulators of Redox-Dependent Processes in Cancer Cell

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Elena V. Kalinina^1,a* and Maria D. Novichkova¹

¹RUDN University, 117198 Moscow, Russia

^* To whom correspondence should be addressed.

Received February 10, 2023; Revised March 10, 2023; Accepted March 11, 2023

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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 S-glutathionylation and S-nitrosylation 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 S-glutathionylated and S-nitrosylated proteins is controlled by the balance between S-glutathionylation/deglutathionylation and S-nitrosylation/denitrosylation, respectively, and depends on the cellular redox status. The extent of S-glutathionylation and S-nitrosylation of protein targets and their ratio largely determine the status and direction of signaling pathways in cancer cells. The review discusses the features of S-glutathionylation and S-nitrosylation reactions and systems that control them in cancer cells, as well as their relationship with redox-dependent processes and tumor growth.

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KEY WORDS: reactive oxygen and nitrogen species, oxidative and nitrosative stress, cancer cells, S-glutathionylation and deglutathionylation, S-nitrosylation, transnitrosylation, denitrosylation

DOI: 10.1134/S0006297923070064

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