Redox-sensitive signaling proteins

Redox-sensitive signaling proteins are a broad class of proteins whose functions are modulated by reversible oxidative modifications, typically occurring at specific cysteine residues [1.1.1, 1.4.1]. These proteins serve as critical sensors and transducers of cellular redox status, converting chemical signals from reactive oxygen species (ROS) into biological responses [1.1.2, 1.5.1]. Key members of this group include transcription factors like Nrf2 and NF-κB, kinases such as p38 MAPK and JNK, and various phosphatases like PTP1B and PTEN [1.1.3, 1.3.1]. Under physiological conditions, these proteins maintain redox homeostasis and regulate processes such as cell proliferation, differentiation, and apoptosis [1.1.1, 1.3.2]. However, their dysregulation is implicated in numerous pathologies, including cancer, where they often promote survival and resistance to therapy, and neurodegenerative diseases characterized by chronic oxidative stress [1.2.1, 1.3.2]. Therapeutic targeting of these proteins involves either activating cytoprotective pathways, such as the Nrf2-mediated antioxidant response, or inhibiting redox-dependent survival signals in diseased cells [1.2.1, 1.3.2]. Current drug candidates include Nrf2 activators like bardoxolone methyl and thioredoxin inhibitors like PX-12 [1.2.1, 1.2.5]. A major challenge in this field is achieving specificity to avoid interfering with essential physiological redox signaling while effectively modulating the disease-associated redox environment [1.3.2, 1.5.1].

Other names

Redox-sensitive proteinsRedox-regulated proteinsThiol-based signaling proteinsRedox sensors

Modulation of cysteine thiol groups through oxidation or reduction [1.1.1, 1.4.1], activation of the Nrf2-mediated antioxidant response pathway [1.3.2], inhibition of pro-inflammatory NF-κB signaling [1.3.2], scavenging of reactive oxygen species [1.2.2], and targeted inhibition of redox-regulating enzymes like thioredoxin reductase [1.2.4].