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CRL3s: The BTB-CUL3-RING E3 Ubiquitin Ligases

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Cullin-RING Ligases and Protein Neddylation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1217))

Abstract

The ubiquitin proteasome pathway is one of the major regulatory tools used by eukaryotic cells. The evolutionarily conserved cullin family proteins can assemble as many as >600 distinct E3 ubiquitin ligase complexes that regulate diverse cellular pathways. In most of Cullin-RING ubiquitin ligase (CRL) complexes, separate linker and adaptor proteins build the substrate recognition module. Differently, a single BTB-containing adaptor molecule utilizing two protein interaction sites can link the CUL3 scaffold to the substrate, forming as many as 188 CUL3-BTB E3 ligase complexes in mammals. Here, we review the most recent studies on CRL3 complexes, with a focus on the model for CUL3 assembly with its BTB-containing substrate receptors. Also, we summarize the current knowledge of CRL3 substrates and their relevant biological functions. Next, we discuss the mutual exclusivity of somatic mutations in KEAP1, NRF2, and CUL3 in human lung cancer. Finally, we highlight new strategies to expand CUL3 substrates and discuss outstanding questions remaining in the field.

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Abbreviations

AID:

Auxin-induced degradation

ANKFY1:

Ankyrin repeat and FYVE domain-containing 1

APC:

Anaphase-promoting complex

ARE:

The antioxidant response element

ATF2:

Activating transcription factor 2

BCL2:

B-cell CLL/lymphoma 2

BTB:

Bric-à-brac, tramtrack and broad

BTB-ZF:

BTB-zinc finger

bTRCP:

Beta-transducin repeat-containing E3 ubiquitin protein ligase

CENP-A:

Centromere protein A

CRL:

Cullin-RING ubiquitin ligase

CRN7:

Coronin 7

CUL:

Cullin

DDB1:

Damage-specific DNA binding protein 1

DWD:

DDB1-binding WD40

eEF1A1:

Eukaryotic translation elongation factor 1 alpha 1

EPS15:

Epidermal growth factor receptor pathway substrate 15

ESCRT:

Endosomal sorting complexes required for transport

FHIT:

Fragile histidine triad gene

GSTA2:

Glutathione S-transferase A2

HECT:

Homologous to the E6-AP Carboxyl Terminus

IVR:

Intervening region

Keap1:

Kelch ECH associating protein 1

KLHDC:

Kelch domain-containing protein

KLHL:

The Kelch-like

LUSC:

Lung squamous cell carcinomas

MEI-1:

Meiosis inhibitor protein 1

MVBs:

Multivesicular bodies

NEDD8:

Neural precursor cell expressed, developmentally downregulated 8

NFE2:

Nuclear factor, erythroid 2

NGS:

Next-generation sequencing

NQO1:

NADPH:quinone oxidoreductase 1

Nrf1:

Nuclear respiratory factor 1

NRF2:

Nuclear factor erythroid 2-related factor 2

NSCLC:

Non-small cell lung cancer

p16 INK4a:

Cyclin-dependent kinase inhibitor 2A

PLK1:

Polo-like kinases 1

Rb1:

Retinoblastoma 1

RBR:

RING-In between-RING

RDX:

Radixin

RING:

Really Interesting New Gene

ROS:

Reactive oxygen species

SCF:

SKP1-CUL1-F-box

SEC31:

Secretory 31

SKP1:

S-Phase kinase associated protein 1

SOCS:

Suppressor of cytokine signaling

SPOP:

Speckle type BTB/POZ protein

SPOPL:

Speckle type BTB/POZ protein like

TGN:

Trans-Golgi network

ULK1:

Unc-51 like autophagy activating kinase 1

WES:

Whole-exome sequencing

WNK4:

WNK lysine deficient protein kinase 4

References

  • Bade D, Pauleau AL, Wendler A, Erhardt S (2014) The E3 ligase CUL3/RDX controls centromere maintenance by ubiquitylating and stabilizing CENP-A in a CAL1-dependent manner. Dev Cell 28:508–519

    Article  CAS  PubMed  Google Scholar 

  • Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ (1996) SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell 86:263–274

    Article  CAS  PubMed  Google Scholar 

  • Bardwell VJ, Treisman R (1994) The POZ domain: a conserved protein-protein interaction motif. Genes Dev 8:1664–1677

    Article  CAS  PubMed  Google Scholar 

  • Beck J, Maerki S, Posch M, Metzger T, Persaud A, Scheel H, Hofmann K, Rotin D, Pedrioli P, Swedlow JR et al (2013) Ubiquitylation-dependent localization of PLK1 in mitosis. Nat Cell Biol 15:430–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonifacino JS, Glick BS (2004) The mechanisms of vesicle budding and fusion. Cell 116:153–166

    Article  CAS  PubMed  Google Scholar 

  • Buetow L, Huang DT (2016) Structural insights into the catalysis and regulation of E3 ubiquitin ligases. Nat Rev Mol Cell Biol 17:626–642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cancer Genome Atlas Research N (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489:519–525

    Article  CAS  Google Scholar 

  • Cancer Genome Atlas Research N (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature 511:543–550

    Article  CAS  Google Scholar 

  • Chaharbakhshi E, Jemc JC (2016) Broad-complex, tramtrack, and bric-a-brac (BTB) proteins: critical regulators of development. Genesis 54:505–518

    Article  CAS  PubMed  Google Scholar 

  • Christ L, Raiborg C, Wenzel EM, Campsteijn C, Stenmark H (2017) Cellular functions and molecular mechanisms of the ESCRT membrane-scission machinery. Trends Biochem Sci 42:42–56

    Article  CAS  PubMed  Google Scholar 

  • Clark-Maguire S, Mains PE (1994a) Localization of the mei-1 gene product of Caenorhabditis elegans, a meiotic-specific spindle component. J Cell Biol 126:199–209

    Article  CAS  PubMed  Google Scholar 

  • Clark-Maguire S, Mains PE (1994b) mei-1, a gene required for meiotic spindle formation in Caenorhabditis elegans, is a member of a family of ATPases. Genetics 136:533–546

    CAS  PubMed  PubMed Central  Google Scholar 

  • Combes G, Alharbi I, Braga LG, Elowe S (2017) Playing polo during mitosis: PLK1 takes the lead. Oncogene 36:4819–4827

    Article  CAS  PubMed  Google Scholar 

  • Cullinan SB, Gordan JD, Jin J, Harper JW, Diehl JA (2004) The Keap1-BTB protein is an adaptor that bridges NRF2 to a Cul3-based E3 ligase: oxidative stress sensing by a Cul3-Keap1 ligase. Mol Cell Biol 24:8477–8486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cummings CM, Bentley CA, Perdue SA, Baas PW, Singer JD (2009) The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is required for normal mitosis in mammalian cells. J Biol Chem 284:11663–11675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dow MR, Mains PE (1998) Genetic and molecular characterization of the caenorhabditis elegans gene, mel-26, a postmeiotic negative regulator of mei-1, a meiotic-specific spindle component. Genetics 150:119–128

    CAS  PubMed  PubMed Central  Google Scholar 

  • Frank R, Scheffler M, Merkelbach-Bruse S, Ihle MA, Kron A, Rauer M, Ueckeroth F, Konig K, Michels S, Fischer R et al (2018) Clinical and pathological characteristics of KEAP1- and NFE2L2-mutated non-small cell lung carcinoma (NSCLC). Clin Cancer Res 24:3087–3096

    Article  CAS  PubMed  Google Scholar 

  • Furukawa M, 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Furukawa M, He YJ, Borchers C, Xiong Y (2003) Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases. Nat Cell Biol 5:1001–1007

    Article  CAS  PubMed  Google Scholar 

  • Geyer R, Wee S, Anderson S, Yates J, Wolf DA (2003) BTB/POZ domain proteins are putative substrate adaptors for cullin 3 ubiquitin ligases. Mol Cell 12:783–790

    Article  CAS  PubMed  Google Scholar 

  • Glotzer M, Murray AW, Kirschner MW (1991) Cyclin is degraded by the ubiquitin pathway. Nature 349:132–138

    Article  CAS  PubMed  Google Scholar 

  • Green RA, Paluch E, Oegema K (2012) Cytokinesis in animal cells. Annu Rev Cell Dev Biol 28:29–58

    Article  CAS  PubMed  Google Scholar 

  • Gschweitl M, Ulbricht A, Barnes CA, Enchev RI, Stoffel-Studer I, Meyer-Schaller N, Huotari J, Yamauchi Y, Greber UF, Helenius A et al (2016) A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomes. Elife 5:e13841

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Haas AL, Warms JV, Hershko A, Rose IA (1982) Ubiquitin-activating enzyme. Mechanism and role in protein-ubiquitin conjugation. J Biol Chem 257:2543–2548

    CAS  PubMed  Google Scholar 

  • Hast BE, Cloer EW, Goldfarb D, Li H, Siesser PF, Yan F, Walter V, Zheng N, Hayes DN, Major MB (2014) Cancer-derived mutations in KEAP1 impair NRF2 degradation but not ubiquitination. Cancer Res 74:808–817

    Article  CAS  PubMed  Google Scholar 

  • He YJ, McCall CM, Hu J, Zeng Y, Xiong Y (2006) DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes Dev 20:2949–2954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hershko A, Heller H, Elias S, Ciechanover A (1983) Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown. J Biol Chem 258:8206–8214

    CAS  PubMed  Google Scholar 

  • Huang G, Kaufman AJ, Xu K, Manova K, Singh B (2017) Squamous cell carcinoma-related oncogene (SCCRO) neddylates Cul3 protein to selectively promote midbody localization and activity of Cul3(KLHL21) protein complex during abscission. J Biol Chem 292:15254–15265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huotari J, Meyer-Schaller N, Hubner M, Stauffer S, Katheder N, Horvath P, Mancini R, Helenius A, Peter M (2012) Cullin-3 regulates late endosome maturation. Proc Natl Acad Sci U S A 109:823–828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, Yamamoto M (1999) Keap1 represses nuclear activation of antioxidant responsive elements by NRF2 through binding to the amino-terminal Neh2 domain. Genes Dev 13:76–86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin L, Pahuja KB, Wickliffe KE, Gorur A, Baumgartel C, Schekman R, Rape M (2012) Ubiquitin-dependent regulation of COPII coat size and function. Nature 482:495–500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamura T, Maenaka K, Kotoshiba S, Matsumoto M, Kohda D, Conaway RC, Conaway JW, Nakayama KI (2004) VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases. Genes Dev 18:3055–3065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Katsuoka F, Motohashi H, Ishii T, Aburatani H, Engel JD, Yamamoto M (2005) Genetic evidence that small maf proteins are essential for the activation of antioxidant response element-dependent genes. Mol Cell Biol 25:8044–8051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • King RW, Peters JM, Tugendreich S, Rolfe M, Hieter P, Kirschner MW (1995) A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell 81:279–288

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi A, Kang MI, Okawa H, Ohtsuji M, Zenke Y, Chiba T, Igarashi K, 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koiwai K, Maezawa S, Hayano T, Iitsuka M, Koiwai O (2008) BPOZ-2 directly binds to eEF1A1 to promote eEF1A1 ubiquitylation and degradation and prevent translation. Genes Cells 13:593–607

    Article  CAS  PubMed  Google Scholar 

  • Kurz T, Pintard L, Willis JH, Hamill DR, Gonczy P, Peter M, Bowerman B (2002) Cytoskeletal regulation by the Nedd8 ubiquitin-like protein modification pathway. Science 295:1294–1298

    Article  CAS  PubMed  Google Scholar 

  • Liu CC, Lin YC, Chen YH, Chen CM, Pang LY, Chen HA, Wu PR, Lin MY, Jiang ST, Tsai TF et al (2016) Cul3-KLHL20 ubiquitin ligase governs the turnover of ULK1 and VPS34 complexes to control autophagy termination. Mol Cell 61:84–97

    Article  CAS  PubMed  Google Scholar 

  • Lo SC, Hannink M (2006) CAND1-mediated substrate adaptor recycling is required for efficient repression of NRF2 by Keap1. Mol Cell Biol 26:1235–1244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lo SC, Li X, Henzl MT, Beamer LJ, Hannink M (2006) Structure of the Keap1:NRF2 interface provides mechanistic insight into NRF2 signaling. EMBO J 25:3605–3617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lyapina SA, Correll CC, Kipreos ET, Deshaies RJ (1998) Human CUL1 forms an evolutionarily conserved ubiquitin ligase complex (SCF) with SKP1 and an F-box protein. Proc Natl Acad Sci U S A 95:7451–7456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma J, Chang K, Peng J, Shi Q, Gan H, Gao K, Feng K, Xu F, Zhang H, Dai B et al (2018) SPOP promotes ATF2 ubiquitination and degradation to suppress prostate cancer progression. J Exp Clin Cancer Res 37:145

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Maeda I, Ohta T, Koizumi H, Fukuda M (2001) In vitro ubiquitination of cyclin D1 by ROC1-CUL1 and ROC1-CUL3. FEBS Lett 494:181–185

    Article  CAS  PubMed  Google Scholar 

  • Maekawa M, Tanigawa K, Sakaue T, Hiyoshi H, Kubota E, Joh T, Watanabe Y, Taguchi T, Higashiyama S (2017) Cullin-3 and its adaptor protein ANKFY1 determine the surface level of integrin beta1 in endothelial cells. Biol Open 6:1707–1719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McIntosh JR (2016) Mitosis. Cold Spring Harb Perspect Biol 8

    Google Scholar 

  • McMahon M, Lamont DJ, Beattie KA, Hayes JD (2010) Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals. Proc Natl Acad Sci U S A 107:18838–18843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Merlet J, Burger J, Gomes JE, Pintard L (2009) Regulation of cullin-RING E3 ubiquitin-ligases by neddylation and dimerization. Cell Mol Life Sci 66:1924–1938

    Article  CAS  PubMed  Google Scholar 

  • Metzger MB, Pruneda JN, Klevit RE, Weissman AM (2014) RING-type E3 ligases: master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination. Biochim Biophys Acta 1843:47–60

    Article  CAS  PubMed  Google Scholar 

  • Metzger T, Kleiss C, Sumara I (2013) CUL3 and protein kinases: insights from PLK1/KLHL22 interaction. Cell Cycle 12:2291–2296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Michel JJ, Xiong Y (1998) Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A. Cell Growth Differ 9:435–449

    CAS  PubMed  Google Scholar 

  • Moghe S, Jiang F, Miura Y, Cerny RL, Tsai MY, Furukawa M (2012) The CUL3-KLHL18 ligase regulates mitotic entry and ubiquitylates Aurora-A. Biol Open 1:82–91

    Article  CAS  PubMed  Google Scholar 

  • Motohashi H, Yamamoto M (2004) NRF2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med 10:549–557

    Article  CAS  PubMed  Google Scholar 

  • Negrini S, Gorgoulis VG, Halazonetis TD (2010) Genomic instability--an evolving hallmark of cancer. Nat Rev Mol Cell Biol 11:220–228

    Article  CAS  PubMed  Google Scholar 

  • Nguyen T, Sherratt PJ, Huang HC, Yang CS, Pickett CB (2003) Increased protein stability as a mechanism that enhances NRF2-mediated transcriptional activation of the antioxidant response element. Degradation of NRF2 by the 26 S proteasome. J Biol Chem 278:4536–4541

    Article  CAS  PubMed  Google Scholar 

  • Nikonova AS, Astsaturov I, Serebriiskii IG, Dunbrack RL Jr, Golemis EA (2013) Aurora A kinase (AURKA) in normal and pathological cell division. Cell Mol Life Sci 70:661–687

    Article  CAS  PubMed  Google Scholar 

  • Ohta T, Michel JJ, Schottelius AJ, Xiong Y (1999) ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. Mol Cell 3:535–541

    Article  CAS  PubMed  Google Scholar 

  • Petroski MD, Deshaies RJ (2005) Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol 6:9–20

    Article  CAS  PubMed  Google Scholar 

  • Pickart CM, Eddins MJ (2004) Ubiquitin: structures, functions, mechanisms. Biochim Biophys Acta 1695:55–72

    Article  CAS  PubMed  Google Scholar 

  • Pickart CM, Rose IA (1985) Functional heterogeneity of ubiquitin carrier proteins. J Biol Chem 260:1573–1581

    CAS  PubMed  Google Scholar 

  • Pintard L, Kurz T, Glaser S, Willis JH, Peter M, Bowerman B (2003a) Neddylation and deneddylation of CUL-3 is required to target MEI-1/Katanin for degradation at the meiosis-to-mitosis transition in C. elegans. Curr Biol 13:911–921

    Article  CAS  PubMed  Google Scholar 

  • Pintard L, Willis JH, Willems A, Johnson JL, Srayko M, Kurz T, Glaser S, Mains PE, Tyers M, Bowerman B et al (2003b) The BTB protein MEL-26 is a substrate-specific adaptor of the CUL-3 ubiquitin-ligase. Nature 425:311–316

    Article  CAS  PubMed  Google Scholar 

  • Rojo de la Vega M, Chapman E, Zhang DD (2018) NRF2 and the hallmarks of Cancer. Cancer Cell 34:21–43

    Article  CAS  PubMed  Google Scholar 

  • Rushmore TH, Morton MR, Pickett CB (1991) The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. J Biol Chem 266:11632–11639

    CAS  PubMed  Google Scholar 

  • Shibata S, Zhang J, Puthumana J, Stone KL, Lifton RP (2013) Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4. Proc Natl Acad Sci USA 110:7838–7843

    Article  CAS  Google Scholar 

  • Singer JD, Gurian-West M, Clurman B, Roberts JM (1999) Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells. Genes Dev 13:2375–2387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh A, Misra V, Thimmulappa RK, Lee H, Ames S, Hoque MO, Herman JG, Baylin SB, Sidransky D, Gabrielson E et al (2006) Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer. PLoS Med 3:e420

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stogios PJ, Downs GS, Jauhal JJ, Nandra SK, Prive GG (2005) Sequence and structural analysis of BTB domain proteins. Genome Biol 6:R82

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sumara I, Quadroni M, Frei C, Olma MH, Sumara G, Ricci R, 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

    Article  CAS  PubMed  Google Scholar 

  • Wakabayashi N, Itoh K, Wakabayashi J, Motohashi H, Noda S, Takahashi S, Imakado S, Kotsuji T, Otsuka F, Roop DR et al (2003) Keap1-null mutation leads to postnatal lethality due to constitutive NRF2 activation. Nat Genet 35:238–245

    Article  CAS  PubMed  Google Scholar 

  • Xu L, Wei Y, Reboul J, Vaglio P, Shin TH, Vidal M, Elledge SJ, Harper JW (2003) BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3. Nature 425:316–321

    Article  CAS  PubMed  Google Scholar 

  • Yesbolatova A, Tominari Y, Kanemaki MT (2019) Ligand-induced genetic degradation as a tool for target validation. Drug Discov Today Technol 31:91–98

    Article  PubMed  Google Scholar 

  • Yuan WC, Lee YR, Lin SY, Chang LY, Tan YP, Hung CC, Kuo JC, Liu CH, Lin MY, Xu M et al (2014) K33-linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 ubiquitin E3 ligase regulates protein trafficking. Mol Cell 54:586–600

    Article  CAS  PubMed  Google Scholar 

  • Zhang DD, Hannink M (2003) Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of NRF2 and for stabilization of NRF2 by chemopreventive agents and oxidative stress. Mol Cell Biol 23:8137–8151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang DD, Lo SC, Cross JV, Templeton DJ, Hannink M (2004) Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Mol Cell Biol 24:10941–10953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng N, Shabek N (2017) Ubiquitin ligases: structure, function, and regulation. Annu Rev Biochem 86:129–157

    Article  CAS  PubMed  Google Scholar 

  • Zhu M, Fahl WE (2001) Functional characterization of transcription regulators that interact with the electrophile response element. Biochem Biophys Res Commun 289:212–219

    Article  CAS  PubMed  Google Scholar 

  • Zhuang M, Calabrese MF, Liu J, Waddell MB, Nourse A, Hammel M, Miller DJ, Walden H, Duda DM, Seyedin SN et al (2009) Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases. Mol Cell 36:39–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zollman S, Godt D, Prive GG, Couderc JL, Laski FA (1994) The BTB domain, found primarily in zinc finger proteins, defines an evolutionarily conserved family that includes several developmentally regulated genes in Drosophila. Proc Natl Acad Sci U S A 91:10717–10721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by the National Key R&D Program of China (No.2016YFA0501800 to D.Y.) and the NSFC grant (No. 31871431, No. 81522033, No. 31821002 to D. Y.).

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Authors and Affiliations

  1. Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China

    Pu Wang, Junbin Song & Dan Ye

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  1. Pu Wang
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  2. Junbin Song
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  3. Dan Ye
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Correspondence to Dan Ye .

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Editors and Affiliations

  1. Radiation Oncology, University of Michigan, Ann Arbor, MI, USA

    Yi Sun

  2. Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Wenyi Wei

  3. Life Science Institute, Zhejiang University, Hangzhou, China

    Jianping Jin

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Wang, P., Song, J., Ye, D. (2020). CRL3s: The BTB-CUL3-RING E3 Ubiquitin Ligases. In: Sun, Y., Wei, W., Jin, J. (eds) Cullin-RING Ligases and Protein Neddylation. Advances in Experimental Medicine and Biology, vol 1217. Springer, Singapore. https://doi.org/10.1007/978-981-15-1025-0_13

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