New strategies to inhibit KEAP1 and the Cul3-based E3 ubiquitin ligases

Biochemical Society Transactions

Volumn 42, Issue 1, 2014, Pages 103-107

  Canning, Peter ^a   Bullock, Alex N ^a,b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Antioxidant response; Cancer; Cell signalling; Degradation; Drug design; Ubiquitylation

Indexed keywords

CULLIN; CULLIN 3; KELCH LIKE ECH ASSOCIATED PROTEIN 1; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMINO TERMINAL SEQUENCE; ARTICLE; DIABETES MELLITUS; ENZYME INHIBITION; OXIDATIVE STRESS; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN DOMAIN; SIGNAL TRANSDUCTION; UBIQUITINATION;

CULLIN PROTEINS; DRUG DESIGN; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MOLECULAR TARGETED THERAPY; MULTIPROTEIN COMPLEXES; PROTEIN STRUCTURE, QUATERNARY; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; UBIQUITINATION;

EID: 84893321146     PISSN: 03005127     EISSN: 14708752     Source Type: Journal    
DOI: 10.1042/BST20130215     Document Type: Article

References (46)

1. Ciechanover, A. and Schwartz, A.L. (1998) The ubiquitin-proteasome pathway: the complexity and myriad functions of proteins death. Proc. Natl. Acad. Sci. U.S.A. 95, 2727-2730
2. Cohen, P. and Tcherpakov, M. (2010) Will the ubiquitin system furnish as many drug targets as protein kinases? Cell 143, 686-693
3. Pickart, C.M. (2001) Mechanisms underlying ubiquitination. Annu. Rev. Biochem. 70, 503-533
4. Petroski, M.D. and Deshaies, R.J. (2005) Function and regulation of Cullin-RING ubiquitin ligases. Nat. Rev. Mol. Cell Biol. 6, 9-20
5. Zheng, N., Schulman, B.A., Song, L., Miller, J.J., Jeffrey, P.D., Wang, P., Chu, C., Koepp, D.M., Elledge, S.J., Pagano, M. et al. (2002) Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature 416, 703-709
6. Duda, D.M., Borg, L.A., Scott, D.C., Hunt, H.W., Hammel, M. and Schulman, B.A. (2008) Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. Cell 134, 995-1006
7. Goldenberg, S.J., Cascio, T.C., Shumway, S.D., Garbutt, K.C., Liu, J., Xiong, Y. and Zheng, N. (2004) Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases. Cell 119, 517-528
8. Ahmad, K.F., Engel, C.K. and Prive, G.G. (1998) Crystal structure of the BTB domain from PLZF. Proc. Natl. Acad. Sci. U.S.A. 95, 12123-12128
9. Stogios, P.J., Downs, G.S., Jauhal, J.J., Nandra, S.K. and Prive, G.G. (2005) Sequence and structural analysis of BTB domain proteins. Genome Biol. 6, R82
10. Sumara, I., Quadroni, M., Frei, C., Olma, M.H., Sumara, G., Ricci, R. and Peter, M. (2007) A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells. Dev. Cell 12, 887-900
11. Maerki, S., Olma, M.H., Staubli, T., Steigemann, P., Gerlich, D.W., Quadroni, M., Sumara, I. and Peter, M. (2009) The Cul3-KLHL21 E3 ubiquitin ligase targets Aurora B to midzone microtubules in anaphase and is required for cytokinesis. J. Cell Biol. 187, 791-800
12. Moghe, S., Jiang, F., Miura, Y., Cerny, R.L., Tsai, M.Y. and Furukawa, M. (2012) The CUL3-KLHL18 ligase regulates mitotic entry and ubiquitylates Aurora-A. Biol. Open 1, 82-91
13. Beck, J. and Peter, M. (2013) Regulating PLK1 dynamics by Cullin3/KLHL22-mediated ubiquitylation. Cell Cycle 12, 2528-2529
14. Yuan, W.-C., Lee, Y.-R., Huang, S.-F., Lin, Y.-M., Chen, T.-Y., Chung, H.-C., Tsai, C.-H., Chen, H.-Y., Chiang, C.-T., Lai, C.-K. et al. (2011) A Cullin3-KLHL20 ubiquitin ligase-dependent pathway targets PML to potentiate HIF-1 signaling and prostate cancer progression. Cancer Cell 20, 214-228
15. Liang, X.Q., Avraham, H.K., Jiang, S. and Avraham, S. (2004) Genetic alterations of the NRP/B gene are associated with human brain tumors. Oncogene 23, 5890-5900
16. Puente, X.S., Pinyol, M., Quesada, V., Conde, L., Ordonez, G.R., Villamor, N., Escaramis, G., Jares, P., Bea, S., Gonzalez-Diaz, M. et al. (2011) Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 475, 101-105
17. Angers, S., Thorpe, C.J., Biechele, T.L., Goldenberg, S.J., Zheng, N., MacCoss, M.J. and Moon, R.T. (2006) The KLHL12-Cullin-3 ubiquitin ligase negatively regulates the Wnt-β-catenin pathway by targeting Dishevelled for degradation. Nat. Cell Biol. 8, 348-357
18. Jin, L., Pahuja, K.B., Wickliffe, K.E., Gorur, A., Baumgartel, C., Schekman, R. and Rape, M. (2012) Ubiquitin-dependent regulation of COPII coat size and function. Nature 482, 495-500
19. Rondou, P., Haegeman, G., Vanhoenacker, P. and Van Craenenbroeck, K. (2008) BTB protein KLHL12 targets the dopamine D4 receptor for ubiquitination by a Cul3-based E3 ligase. J. Biol. Chem. 283, 11083-11096
20. Shibata, S., Zhang, J., Puthumana, J., Stone, K.L. and Lifton, R.P. (2013) Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4. Proc. Natl. Acad. Sci. U.S.A. 110, 7838-7843
21. Ohta, A., Schumacher, F.R., Mehellou, Y., Johnson, C., Knebel, A., Macartney, T.J., Wood, N.T., Alessi, D.R. and Kurz, T. (2013) The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction. Biochem. J. 451, 111-122
22. Wakabayashi, M., Mori, T., Isobe, K., Sohara, E., Susa, K., Araki, Y., Chiga, M., Kikuchi, E., Nomura, N., Mori, Y. et al. (2013) Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension. Cell Rep. 3, 858-868
23. Kigoshi, Y., Tsuruta, F. and Chiba, T. (2011) Ubiquitin ligase activity of Cul3-KLHL7 protein is attenuated by autosomal dominant retinitis pigmentosa causative mutation. J. Biol. Chem. 286, 33613-33621
24. Cirak, S., von Deimling, F., Sachdev, S., Errington, W.J., Herrmann, R., Bönnemann, C., Brockmann, K., Hinderlich, S., Lindner, T.H., Steinbrecher, A. et al. (2010) Kelch-like homologue 9 mutation is associated with an early onset autosomal dominant distal myopathy. Brain 133, 2123-2135
25. Bomont, P., Cavalier, L., Blondeau, F., Ben Hamida, C., Belal, S., Tazir, M., Demir, E., Topaloglu, H., Korinthenberg, R., Tuysuz, B. et al. (2000) The gene encoding gigaxonin, a new member of the cytoskeletal BTB/Kelch repeat family, is mutated in giant axonal neuropathy. Nat. Genet. 26, 370-374
26. Ravenscroft, G., Miyatake, S., Lehtokari, V.L., Todd, E.J., Vornanen, P., Yau, K.S., Hayashi, Y.K., Miyake, N., Tsurusaki, Y., Doi, H. et al. (2013) Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy. Am. J. Hum. Genet. 93, 6-18
27. Kobayashi, A., Kang, M.I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., Igarashi, K. and Yamamoto, M. (2004) Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol. Cell. Biol. 24, 7130-7139
28. Furukawa, M. and Xiong, Y. (2005) BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase. Mol. Cell. Biol. 25, 162-171
29. McMahon, M., Itoh, K., Yamamoto, M. and Hayes, J.D. (2003) Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J. Biol. Chem. 278, 21592-21600
30. Zhuang, M., Calabrese, M.F., Liu, J., Waddell, M.B., Nourse, A., Hammel, M., Miller, D.J., Walden, H., Duda, D.M., Seyedin, S.N. et al. (2009) Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases. Mol. Cell 36, 39-50
31. Canning, P., Cooper, C.D., Krojer, T., Murray, J.W., Pike, A.C., Chaikuad, A., Keates, T., Thangaratnarajah, C., Hojzan, V., Marsden, B.D. et al. (2013) Structural basis for Cul3 protein assembly with the BTB-Kelch family of E3 ubiquitin ligases. J. Biol. Chem. 288, 7803-7814
32. Errington, W.J., Khan, M.Q., Bueler, S.A., Rubinstein, J.L., Chakrabartty, A. and Privé, G.G. (2012) Adaptor protein self-assembly drives the control of a Cullin-RING ubiquitin ligase. Structure 20, 1141-1153
33. McMahon, M., Thomas, N., Itoh, K., Yamamoto, M. and Hayes, J.D. (2006) Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a "tethering" mechanism: a two-site interaction model for the Nrf2-Keap1 complex. J. Biol. Chem. 281, 24756-24768
34. Ogura, T., Tong, K.I., Mio, K., Maruyama, Y., Kurokawa, H., Sato, C. and Yamamoto, M. (2010) Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycine repeat, and C-terminal domains. Proc. Natl. Acad. Sci. U.S.A. 107, 2842-2847
35. Tong, K.I., Padmanabhan, B., Kobayashi, A., Shang, C., Hirotsu, Y., Yokoyama, S. and Yamamoto, M. (2007) Different electrostatic potentials define ETGE and DLG motifs as hinge and latch in oxidative stress response. Mol. Cell. Biol. 27, 7511-7521
36. Tong, K.I., Katoh, Y., Kusunoki, H., Itoh, K., Tanaka, T. and Yamamoto, M. (2006) Keap1 recruits Neh2 through binding to ETGE and DLG motifs: characterization of the two-site molecular recognition model. Mol. Cell. Biol. 26, 2887-2900
37. Ji, A.X. and Privé, G.G. (2013) Crystal structure of KLHL3 in complex with Cullin3. PLoS ONE 8, e60445
38. Suzuki, T., Motohashi, H. and Yamamoto, M. (2013) Toward clinical application of the Keap1-Nrf2 pathway. Trends Pharmacol. Sci. 34, 340-346
39. Hur, W., Sun, Z., Jiang, T., Mason, D.E., Peters, E.C., Zhang, D.D., Luesch, H., Schultz, P.G. and Gray, N.S. (2010) A small-molecule inducer of the antioxidant response element. Chem. Biol. 17, 537-547
40. Sekhar, K.R., Rachakonda, G. and Freeman, M.L. (2010) Cysteine-based regulation of the CUL3 adaptor protein Keap1. Toxicol. Appl. Pharmacol. 244, 21-26
41. Hu, L., Magesh, S., Chen, L., Wang, L., Lewis, T.A., Chen, Y., Khodier, C., Inoyama, D., Beamer, L.J., Emge, T.J. et al. (2013) Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interaction. Bioorg. Med. Chem. Lett. 23, 3039-3043
42. Magesh, S., Chen, Y. and Hu, L. (2012) Small molecule modulators of Keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents. Med. Res. Rev. 32, 687-726
43. Marcotte, D., Zeng, W., Hus, J.-C., McKenzie, A., Hession, C., Jin, P., Bergeron, C., Lugovskoy, A., Enyedy, I., Cuervo, H. et al. (2013) Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism. Bioorg. Med. Chem. 21, 4011-4019
44. Hancock, R., Schaap, M., Pfister, H. and Wells, G. (2013) Peptide inhibitors of the Keap1-Nrf2 protein-protein interaction with improved binding and cellular activity. Org. Biomol. Chem. 11, 3553-3557
45. Lo, S.C., Li, X., Henzl, M.T., Beamer, L.J. and Hannink, M. (2006) Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling. EMBO J. 25, 3605-3617
46. Hu, L., Magesh, S., Chen, L., Wang, L., Lewis, T.A., Chen, Y., Khodier, C., Inoyama, D., Beamer, L.J., Emge, T.J. et al. (2013) Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interaction. Bioorg. Med. Chem. Lett. 23, 3039-3043