S-glutathionylation and S-nitrosylation as modulators of redox-dependent processes in cancer cell

Abstract

The development of oxidative/nitrosative stress associated with the activation of oncogenic pathways is a consequence of an increase in the level of generation of reactive oxygen and nitrogen species (ROS/RNS) in tumor cells. The action of ROS/RNS is dual: high levels cause cell death and limit tumor growth at certain phases of malignant neoplasm development, while low concentrations allow oxidative/nitrosative modifications of key redox-dependent residues in regulatory proteins. The reversibility of such modifications as S-glutathionylation/S-nitrosylation, which occur through the electrophilic attack of ROS/RNS on the nucleophilic residues of Cys, provides redox switching in the activity of signaling proteins and the ability to control the processes of proliferation and programmed death. The level of S-glutathionylated and S-nitrosylated proteins is controlled by the balance between S-glutathionylation/deglutathionylation and S-nitrosylation/denitrosylation, the ratio of which depends on the cellular redox status. The degree of S-glutathionylation and S-nitrosylation of protein targets and their ratio largely determines the state and directions of signaling pathways in cancer cells. The review discusses the features of S-glutathionylation and S-nitrosylation reactions in cancer cells, the balance of systems that control their activity and their relationship with redox-dependent processes and tumor growth.