GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2

Baird L, Yamamoto M. The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway. Molecular and Cellular Biology. 2020 Jun 15;40(13). doi: 10.1128/mcb.00099-20.; Chen Y, Liu K, Zhang J, Hai Y, Wang P, Wang H, Liu Q, Wong CCL, Yao J, Gao Y, Liao Y, Tang X, Wang XJ. c-Jun NH2 -Terminal Protein Kinase Phosphorylates the Nrf2-ECH Homology 6 Domain of Nuclear Factor Erythroid 2-Related Factor 2 and Downregulates Cytoprotective Genes in Acetaminophen-Induced Liver Injury in Mice. Hepatology. 2020 May;71(5):1787–801. PMID: 31945188; PMCID: PMC7318587.; Yamamoto M, Kensler TW, Motohashi H. The KEAP1-NRF2 System: a Thiol-Based Sensor-Effector Apparatus for Maintaining Redox Homeostasis. Physiological Reviews. 2018 Jul 01;98(3):1169–203. doi: 10.1152/physrev.00023.2017.; Cuadrado A. Structural and functional characterization of Nrf2 degradation by glycogen synthase kinase 3/ß-TrCP. Free Radic Biol Med. 2015 Nov;88(Pt B):147–57. doi: 10.1016/j.freeradbiomed.2015.04.029. PMID: 25937177.; Rada P, Rojo AI, Evrard-Todeschi N, Innamorato NG, Cotte A, Jaworski T, Tobón-Velasco JC, Devijver H, García-Mayoral MF, Van Leuven F, Hayes JD, Bertho G, Cuadrado A. Structural and Functional Characterization of Nrf2 Degradation by the Glycogen Synthase Kinase 3/ß-TrCP Axis. Molecular and Cellular Biology. 2012 Sep 01;32(17):3486–99. doi: 10.1128/mcb.00180-12.; Rojo AI, Medina-Campos ON, Rada P, Zúñiga-Toalá A, López-Gazcón A, Espada S, Pedraza-Chaverri J, Cuadrado A. Signaling pathways activated by the phytochemical nordihydroguaiaretic acid contribute to a Keap1-independent regulation of Nrf2 stability: Role of glycogen synthase kinase-3. Free Radic Biol Med. 2012 Jan 15;52(2):473–87. doi: 10.1016/j.freeradbiomed.2011.11.003. PMID: 22142471.; Rada P, Rojo AI, Chowdhry S, McMahon M, Hayes JD, Cuadrado A. SCF/ß-TrCP Promotes Glycogen Synthase Kinase 3-Dependent Degradation of the Nrf2 Transcription Factor in a Keap1-Independent Manner. Molecular and Cellular Biology. 2011 Mar 01;31(6):1121–33. doi: 10.1128/mcb.01204-10.; Salazar M, Rojo AI, Velasco D, de Sagarra RM, Cuadrado A. Glycogen synthase kinase-3beta inhibits the xenobiotic and antioxidant cell response by direct phosphorylation and nuclear exclusion of the transcription factor Nrf2. J Biol Chem. 2006 May 26;281(21):14841–51. doi: 10.1074/jbc.m513737200. PMID: 16551619.

Metabolites

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
2.3.2.27 RING-type E3 ubiquitin transferase [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (isopeptide bond-forming; RING-type)
2.3.2.32 cullin-RING-type E3 NEDD8 transferase [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine:[cullin] [NEDD8-protein] transferase (isopeptide bond-forming; RING-type)
2.7.11.1 non-specific serine/threonine protein kinase ATP:protein phosphotransferase (non-specific)
2.7.11.26 tau-protein kinase ATP:[tau-protein] O-phosphotransferase


Proteins

Protein ID name full name