CncC/Maf‐mediated xenobiotic response pathway in insects

Insects have evolved resistance to almost all insecticides developed for their control. Multiple mechanisms of resistance, including enhanced metabolism and excretion of insecticides, target‐site insensitivity, reduced penetration of insecticides, and avoidance behavior, have been reported. The genes coding for proteins involved in resistance have been identified in numerous insects. The enzymes and transporters required for all three phases of insecticide metabolism and excretion including cytochrome P450 monooxygenases, glutathione S‐transferases, UDP‐glucuronosyltransferases, carboxylesterases, and ATP‐binding cassette transmembrane transporters have been identified. Recent research in multiple insect species identified CNC‐bZIP transcription factor superfamily members as regulators of genes coding for enzymes and transporters involved in insecticide metabolic resistance. The information on the pathway including reactive oxygen species, cap “n” collar isoform‐C, and its heterodimer partner, muscle aponeurosis fibromatosis transcription factors involved in overexpression of enzymes and transporters involved insecticide resistance will be summarized. A model for cap “n” collar isoform‐C (CncC) and muscle aponeurosis fibromatosis (Maf) regulation of xenobiotic response genes. CncC heterodimerizes with Kelch‐like ECH‐associated protein 1 (Keap1) and stays in the cytoplasm anchored to actin filaments. Under xenobiotic stress conditions, reactive oxygen species (ROS) or other molecules induce dissociation of CncC and Keap1 allowing CncC to translocate to the nucleus and heterodimerize with Maf. The heterodimer binds to CncC/Maf response elements located in the promoter of xenobiotic response genes and induces their expression. Research Highlights CNC‐bZIP transcription factor superfamily members regulate genes coding for enzymes involved in xenobiotic response. Cap “n” collar isoform‐Coform‐C (CncC) and muscle aponeurosis fibromatosis (Maf) induce expression of genes coding for enzymes and transporters involved insecticide resistance.