Elsevier Inc. Gsk3b electrophiles ---| Pten ROS ---| Pten electrophiles ROS Keap1 Btrc mTorc1 complex Pten environmental cues cellular stresses Nfe2l2 target genes Kelch-repeat Neh6 Cul3/Rbx1 complex ---| Nfe2l2 Skp1/Cul1/Rbx1 complex ---| Nfe2l2 Cul3/Rbx1 complex ---> Nfe2l2 Keap1 ---- Nfe2l2 small MAFs mTOR signaling pathway <++> phosphatidylinositol 3-kinase-Akt signaling pathway cellular stresses --+> phosphatidylinositol 3-kinase-Akt signaling pathway environmental cues --+> mTOR signaling pathway Skp1/Cul1/Rbx1 complex ---> Nfe2l2 Gsk3b --+> Btrc Crebbp ROS ---| Keap1 electrophiles ---| Keap1 nuclear Nfe2l2 nuclear Nfe2l2 ---- small MAFs Neh2 ---- Neh3 Neh1 BTB ---> CTR Gsk3b ---> Nfe2l2 Gsk3a ---> Nfe2l2 Btrc ---- Nfe2l2 phosphatidylinositol 3-kinase-Akt signaling pathway ---> Gsk3b phosphatidylinositol 3-kinase-Akt signaling pathway ---| Gsk3b phosphatidylinositol 3-kinase-Akt signaling pathway ---| Gsk3a phosphatidylinositol 3-kinase-Akt signaling pathway ---> Gsk3a IVR Gsk3a ROS --+> nuclear Nfe2l2 electrophiles --+> nuclear Nfe2l2 nuclear Nfe2l2 ---> Nfe2l2 target genes small MAFs ---> Nfe2l2 target genes Pten --+> Gsk3b Pten ---> Gsk3b Pten --+> Gsk3a Pten ---> Gsk3a C226/C613 preferring C273/C288 preferring C434 preferring CTR Skp1/Cul1/Rbx1 complex Nfe2l2 Nfe2l2 interactors ---> Nfe2l2 Keap1 ---- Keap1 interactors Keap1 interactors ---| Keap1 mTorc1 complex ---> Sqstm1 mTorc1 complex --+> Sqstm1 Neh7 Crebbp ---- Neh5 Crebbp ---- Neh4 Neh4 Neh5 Ncoa3 ---- Neh5 Ncoa3 ---- Neh4 Nfe2l2 ---- Nfe2l2 interactors Ncoa3 Chd6 Neh3 Chd6 ---- Neh3 C151 preferring 3-box BTB Neh2 mTOR signaling pathway phosphatidylinositol 3-kinase-Akt signaling pathway Cul3/Rbx1 complex Sqstm1 Keap1 interactors Nfe2l2 interactors