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