Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex
Abstract
SCF complexes are the largest family of E3 ubiquitin-protein ligases and mediate the ubiquitination of diverse regulatory and signalling proteins. Here we present the crystal structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF complex, which shows that Cul1 is an elongated protein that consists of a long stalk and a globular domain. The globular domain binds the RING finger protein Rbx1 through an intermolecular beta-sheet, forming a two-subunit catalytic core that recruits the ubiquitin-conjugating enzyme. The long stalk, which consists of three repeats of a novel five-helix motif, binds the Skp1-F boxSkp2 protein substrate-recognition complex at its tip. Cul1 serves as a rigid scaffold that organizes the Skp1-F boxSkp2 and Rbx1 subunits, holding them over 100 A apart. The structure suggests that Cul1 may contribute to catalysis through the positioning of the substrate and the ubiquitin-conjugating enzyme, and this model is supported by Cul1 mutations designed to eliminate the rigidity of the scaffold.
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A well-resolved substrate scaffolding module in the cryo EM reconstructions resembles models based on crystal structures of substrate-bound SKP1-β-TRCP and the portion of an F-box-SKP1-CUL1-RBX1 complex including CUL1's N-terminal domain and the intermolecular C/R domain.
“A well-resolved “substrate scaffolding module” resembles models based on crystal structures of substrate-bound SKP1-β-TRCP and the portion of an F-box-SKP1-CUL1-RBX1 complex including CUL1’s N-terminal domain and the intermolecular C/R domain7,20.”
From NEDD8 nucleates a multivalent cullin–RING–UBE2D ubiquitin ligation assembly (2020) · cites this paper as [7]
UB transfer from a RING-docked UBE2D~UB intermediate to an F-box protein-bound substrate is difficult to rationalize by prior structural models or by the paper's cryo EM reconstructions of unneddylated and neddylated substrate-bound CRL1β-TRCP.
“UB transfer from a RING-docked UBE2D~UB intermediate (“~” indicates thioester bond/thioester-bond mimic) to an F-box protein-bound substrate is difficult to rationalize by prior structural models 3,7,20,27, or by our cryo EM reconstructions of unneddylated and neddylated substrate-bound CRL1β-TRCP”
From NEDD8 nucleates a multivalent cullin–RING–UBE2D ubiquitin ligation assembly (2020) · cites this paper as [7]
The original CUL1-RBX1 structure (PDB ID 1LDJ) is dynamic.
“the original CUL1-RBX1 structure (PDB ID 1LDJ, “Pre-Neddylation”, which data herein shows is dynamic, although the crystal structure likely captured the conformation allowing CAND1 binding and substrate receptor exchange)7”
From NEDD8 nucleates a multivalent cullin–RING–UBE2D ubiquitin ligation assembly (2020) · cites this paper as [7]
Cryo EM density from the neddylated CRL1β-TRCP-UBE2D~UB-substrate intermediate complex shows patchiness of the region corresponding to CUL1 "Helix-29".
“Cryo EM density from the neddylated CRL1β-TRCP-UBE2D~UB-substrate intermediate complex, showing patchiness of region corresponding to CUL1 “Helix-29”7.”
From NEDD8 nucleates a multivalent cullin–RING–UBE2D ubiquitin ligation assembly (2020) · cites this paper as [7]
Cryo-EM density from the neddylated CRL1β-TRCP-UBE2D~UB-substrate intermediate complex shows patchiness of the region corresponding to CUL1 Helix-29.
“EM density from the neddylated CRL1β-TRCP-UBE2D~UB-substrate intermediate complex, showing patchiness of region corresponding to CUL1 “Helix-29”7.”
From NEDD8 nucleates a multivalent cullin–RING–UBE2D ubiquitin ligation assembly (2020) · cites this paper as [7]
Refined cryo EM density from CRL1β-TRCP reveals a substrate scaffolding module bridging the substrate recruited to substrate receptor β-TRCP with the intermolecular cullin-RBX (C/R) domain.
“Refined cryo EM density from CRL1β-TRCP reveals substrate scaffolding module bridging the substrate recruited to substrate receptor β-TRCP with the intermolecular cullin-RBX (C/R) domain, readily fitted with crystal structures of SKP1-β-TRCP [PDB: 1P22]20 and CUL1’s N-terminal domain and the C/R domain of CUL1-RBX1 [PDB: 1LDK]7.”
From NEDD8 nucleates a multivalent cullin–RING–UBE2D ubiquitin ligation assembly (2020) · cites this paper as [7]
Cites
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475 · see citing works
The CCP4 suite: programs for protein crystallography
Number Collaborative Computational Project (1994) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444994003112 · Cited by 17,299 · see citing works
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination
Brünger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse‐Kunstleve, R. W., Jiang, J., Kuszewski, J. J., Nilges, M., Pannu, N., et al. (1998) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998003254 · Cited by 15,720 · see citing works
MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures
Kraulis, P. J. (1991) · Journal of Applied Crystallography · doi:10.1107/s0021889891004399 · Cited by 14,157 · see citing works
Jones, T. A., Zou, J.-Y., Cowan, S. W., & Kjeldgaard, M. (1991) · Acta Crystallographica Section A Foundations of Crystallography · doi:10.1107/s0108767390010224 · Cited by 12,650 · see citing works
Hershko, A., & Ciechanover, A. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.425 · Cited by 8,840 · see citing works
Nicholls, A. O., Sharp, K. A., & Honig, B. H. (1991) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340110407 · Cited by 5,253 · see citing works
Mechanisms Underlying Ubiquitination
Pickart, C. M. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.503 · Cited by 3,731 · see citing works
Polakis, P. (2000) · Genes & Development · doi:10.1101/gad.14.15.1837 · Cited by 3,183 · see citing works
Identification of the von Hippel-Lindau Disease Tumor Suppressor Gene
Latif, F., Tory, K., Gnarra, J. R., Yao, M., Duh, F.-M. C., Orcutt, M. L., Stackhouse, T. M., Kuzmin, I., Modi, W. S., Geil, L., et al. (1993) · Science · doi:10.1126/science.8493574 · Cited by 2,971 · see citing works
Fortelle, E. D. L., & Bricogne, G. (1997) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(97)76073-7 · Cited by 1,893 · see citing works
Bai, C., Sen, P., Hofmann, K., Ma, L., Goebl, M. G., Harper, J. W., & Elledge, S. J. (1996) · Cell · doi:10.1016/s0092-8674(00)80098-7 · Cited by 1,421 · see citing works
Self-citationJoazeiro, C. A. P., & Weissman, A. M. (2000) · Cell · doi:10.1016/s0092-8674(00)00077-5 · Cited by 1,249 · see citing works
SCF and Cullin/RING H2-Based Ubiquitin Ligases
Deshaies, R. J. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.435 · Cited by 1,238 · see citing works
Skowyra, D., Craig, K. L., Tyers, M., Elledge, S. J., & Harper, J. W. (1997) · Cell · doi:10.1016/s0092-8674(00)80403-1 · Cited by 1,227 · see citing works
Self-citationCrystal structure of the p27Kip1 cyclin-dependent-kinase inibitor bound to the cyclin A–Cdk2 complex
Russo, A. A., Jeffrey, P. D., Patten, A. K., Massagué, J., & Pavletich, N. P. (1996) · Nature · doi:10.1038/382325a0 · Cited by 907 · see citing works
Self-citationFeldman, R. M. R., Correll, C. C., Kaplan, K. B., & Deshaies, R. J. (1997) · Cell · doi:10.1016/s0092-8674(00)80404-3 · Cited by 872 · see citing works
Structure of the VHL-ElonginC-ElonginB Complex: Implications for VHL Tumor Suppressor Function
Stebbins, C. E., Kaelin, W. G., & Pavletich, N. P. (1999) · Science · doi:10.1126/science.284.5413.455 · Cited by 852 · see citing works
Self-citationStructure of a c-Cbl–UbcH7 Complex
Zheng, N., Wang, P., Jeffrey, P. D., & Pavletich, N. P. (2000) · Cell · doi:10.1016/s0092-8674(00)00057-x · Cited by 839 · see citing works
Self-citationRbx1, a Component of the VHL Tumor Suppressor Complex and SCF Ubiquitin Ligase
Kamura, T., Koepp, D. M., Conrad, M. N., Skowyra, D., Moreland, R. J., Iliopoulos, O., Lane, W. S., Kaelin, W. G., Elledge, S. J., Conaway, R. C., et al. (1999) · Science · doi:10.1126/science.284.5414.657 · Cited by 786 · see citing works
Self-citationPhosphorylation-Dependent Ubiquitination of Cyclin E by the SCF Fbw7 Ubiquitin Ligase
Koepp, D. M., Schaefer, L. K., Ye, X., Keyomarsi, K., Chu, C., Harper, J. W., & Elledge, S. J. (2001) · Science · doi:10.1126/science.1065203 · Cited by 764 · see citing works
Self-citationKipreos, E. T., & Pagano, M. (2000) · Genome biology · doi:10.1186/gb-2000-1-5-reviews3002 · Cited by 743 · see citing works
Self-citationInsights into SCF ubiquitin ligases from the structure of the Skp1–Skp2 complex
Schulman, B. A., Carrano, A. C., Jeffrey, P. D., Bowen, Z., Kinnucan, E., Finnin, M. S., Elledge, S. J., Harper, J. W., Pagano, M., & Pavletich, N. P. (2000) · Nature · doi:10.1038/35042620 · Cited by 610 · see citing works
Self-citationStrohmaier, H. M., Spruck, C., Kaiser, P., Won, K., Sangfelt, O., & Reed, S. I. (2001) · Nature · doi:10.1038/35095076 · Cited by 584 · see citing works
Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination.
Scherer, D. C., Brockman, J. A., Chen, Z., Maniatis, T., & Ballard, D. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.24.11259 · Cited by 554 · see citing works
Skp2 is oncogenic and overexpressed in human cancers
Gstaiger, M., Jordan, R. C., Lim, M. S., Catzavelos, C., Mestan, J., Slingerland, J. M., & Krek, W. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081474898 · Cited by 508 · see citing works
The cell-cycle regulatory protein Cks1 is required for SCFSkp2-mediated ubiquitinylation of p27
Ganoth, D., Bornstein, G., Ko, T. K., Larsen, B. G., Tyers, M., Pagano, M., & Hershko, A. (2001) · Nature Cell Biology · doi:10.1038/35060126 · Cited by 468 · see citing works
Self-citationOhta, T., Michel, J. J. C., Schottelius, A. J. G., & Xiong, Y. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80482-7 · Cited by 461 · see citing works
cul-1 Is Required for Cell Cycle Exit in C. elegans and Identifies a Novel Gene Family
Kipreos, E. T., Lander, L. E., Wing, J. P., He, W. W., & Hedgecock, E. M. (1996) · Cell · doi:10.1016/s0092-8674(00)81267-2 · Cited by 448 · see citing works
How the Cyclin Became a Cyclin
Koepp, D. M., Harper, J. W., & Elledge, S. J. (1999) · Cell · doi:10.1016/s0092-8674(00)80753-9 · Cited by 445 · see citing works
Self-citationArchipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines
Moberg, K. H., Bell, D. W., Wahrer, D. C. R., Haber, D. A., & Hariharan, I. K. (2001) · Nature · doi:10.1038/35095068 · Cited by 438 · see citing works
Seol, J. H., Feldman, R. M. R., Zachariae, W., Shevchenko, A., Correll, C. C., Lyapina, S., Chi, Y., Gálová, M., Claypool, J. T., Sandmeyer, S. B., et al. (1999) · Genes & Development · doi:10.1101/gad.13.12.1614 · Cited by 403 · see citing works
Reconstitution of G 1 Cyclin Ubiquitination with Complexes Containing SCF Grr1 and Rbx1
Skowyra, D., Koepp, D. M., Kamura, T., Conrad, M. N., Conaway, R. C., Conaway, J. W., Elledge, S. J., & Harper, J. W. (1999) · Science · doi:10.1126/science.284.5414.662 · Cited by 377 · see citing works
Self-citationNedd8 Modification of Cul-1 Activates SCF<sup>βTrCP</sup>-Dependent Ubiquitination of IκBα
Read, M. A., Brownell, J. E., Gladysheva, T. B., Hottelet, M., Parent, L. A., Coggins, M. B., Pierce, J. W., Podust, V. N., Luo, R.-S., Chau, V., et al. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.7.2326-2333.2000 · Cited by 363 · see citing works
A CDK-Independent Function of Mammalian Cks1
Spruck, C., Strohmaier, H. M., Watson, M. H., Smith, A. P. L., Ryan, A., Krek, W., & Reed, S. I. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00210-6 · Cited by 355 · see citing works
NEDD8 recruits E2‐ubiquitin to SCF E3 ligase
Kawakami, T., Chiba, T., Suzuki, T., Iwai, K., Yamanaka, K., Minato, N., Suzuki, H., Shimbara, N., Hidaka, Y., Osaka, F., et al. (2001) · EMBO Journal · doi:10.1093/emboj/20.15.4003 · Cited by 344 · see citing works
Zachariae, W., Shevchenko, A., Andrews, P. D., Ciosk, R., Gálová, M., Stark, M. J. R., Mann, M., & Nasmyth, K. (1998) · Science · doi:10.1126/science.279.5354.1216 · Cited by 326 · see citing works
Role of the F-box protein Skp2 in lymphomagenesis
Latres, E., Chiarle, R., Schulman, B. A., Pavletich, N. P., Pellicer, À., Inghirami, G., & Pagano, M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.041475098 · Cited by 277 · see citing works
Self-citationPatton, E. E., Willems, A. R., Sa, D., Kuras, L., Thomas, D., Craig, K. L., & Tyers, M. (1998) · Genes & Development · doi:10.1101/gad.12.5.692 · Cited by 270 · see citing works
Identification of a Cullin Homology Region in a Subunit of the Anaphase-Promoting Complex
Yu, H., Peters, J., King, R. W., Page, A. M., Hieter, P., & Kirschner, M. W. (1998) · Science · doi:10.1126/science.279.5354.1219 · Cited by 248 · see citing works
Down-regulation of p27 by Two Mechanisms, Ubiquitin-mediated Degradation and Proteolytic Processing
Shirane, M., Harumiya, Y., Ishida, N., Hirai, A., Miyamoto, C., Hatakeyama, S., Nakayama, K. I., & Kitagawa, M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.20.13886 · Cited by 226 · see citing works
Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoNPreprint
Stroschein, S. L., Bonni, S., Wrana, J. L., & Luo, K. (2001) · Genes & Development · doi:10.1101/gad.912901 · Cited by 218 · see citing works
The von Hippel–Lindau tumor suppressor protein
Ivan, M., & Kaelin, W. G. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00152-0 · Cited by 211 · see citing works
Mathias, N., Johnson, S. L., Winey, M., et al. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.12.6634 · Cited by 197 · see citing works
Morimoto, M., Nishida, T., Honda, R., & Yasuda, H. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2576 · Cited by 134 · see citing works
Crystal Structure of the Vesicular Transport Protein Sec17
Rice, L. M., & Brünger, A. T. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80190-2 · Cited by 112 · see citing works
Characterization of the DOC1/APC10 Subunit of the Yeast and the Human Anaphase-promoting Complex
Grossberger, R., Gieffers, C., Zachariae, W., Podtelejnikov, A. V., Schleiffer, A., Nasmyth, K., Mann, M., & Peters, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.20.14500 · Cited by 96 · see citing works
Human three-dimensional fibroblast cultures express angiogenic activity
Pinney, E., Liu, K., Sheeman, B., & Mansbridge, J. N. (2000) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(200004)183:1 · Cited by 94 · see citing works
Wu, K. K.-Y., Chen, A., Tan, P., & Pan, Z. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108008200 · Cited by 82 · see citing works
The Conserved RING-H2 Finger of ROC1 Is Required for Ubiquitin Ligation
Chen, A., Wu, K. K.-Y., Fuchs, S. Y., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m907300199 · Cited by 64 · see citing works
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Deshaies, R. J., & Joazeiro, C. A. P. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.101807.093809 · Cited by 2,679 · see citing works
Kobayashi, A., Kang, M.-I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., Igarashi, K., & Yamamoto, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.16.7130-7139.2004 · Cited by 2,224 · see citing works
Function and regulation of cullin–RING ubiquitin ligases
Petroski, M. D., & Deshaies, R. J. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1547 · Cited by 2,148 · see citing works
Mechanism of auxin perception by the TIR1 ubiquitin ligase
Tan, X., Calderon-Villalobos, L. I. A., Sharon, M., Zheng, C., Robinson, C. V., Estelle, M., & Zheng, N. (2007) · Nature · doi:10.1038/nature05731 · Cited by 1,688 · see citing works
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Zheng, N., & Shabek, N. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014922 · Cited by 1,499 · see citing works
The SCF ubiquitin ligase: insights into a molecular machine
Cardozo, T., & Pagano, M. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1471 · Cited by 1,114 · see citing works
Self-citationWelcker, M., & Clurman, B. E. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2290 · Cited by 1,084 · see citing works
Lu, H., Zhou, Q., He, J., Jiang, Z., Peng, C., Tong, R., & Shi, J. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00315-3 · Cited by 891 · see citing works
Cellular and Molecular Basis of Deiodinase-Regulated Thyroid Hormone Signaling1
Gereben, B., Zavacki, A. M., Ribich, S., Kim, B. W., Huang, S. A., Simonides, W. S., Zeöld, A., & Bianco, A. C. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0019 · Cited by 891 · see citing works
Vinuesa, C. G., Cook, M. C., Angelucci, C., Athanasopoulos, V., Rui, L., Hill, K. M., Yu, D., Domaschenz, H., Whittle, B., Lambe, T., et al. (2005) · Nature · doi:10.1038/nature03555 · Cited by 862 · see citing works
Duda, D. M., Borg, L. A., Scott, D. C., Hunt, H. W., Hammel, M., & Schulman, B. A. (2008) · Cell · doi:10.1016/j.cell.2008.07.022 · Cited by 767 · see citing works
Self-citationTong, K. I., Katoh, Y., Kusunoki, H., Itoh, K., Tanaka, T., & Yamamoto, M. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.8.2887-2900.2006 · Cited by 759 · see citing works
Sequence and structural analysis of BTB domain proteins
Stogios, P. J., Downs, G. S., Jauhal, J. J., Nandra, S. K., & Privé, G. G. (2005) · Genome Biology · doi:10.1186/gb-2005-6-10-r82 · Cited by 694 · see citing works
Molecular architecture and assembly of the DDB1–CUL4A ubiquitin ligase machinery
Angers, S., Li, T., Yi, X., MacCoss, M. J., Moon, R. T., & Zheng, N. (2006) · Nature · doi:10.1038/nature05175 · Cited by 674 · see citing works
Self-citationJin, J., Arias, E. E., Chen, J., Harper, J. W., & Walter, J. C. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.08.010 · Cited by 632 · see citing works
Self-citationStructure of a β-TrCP1-Skp1-β-Catenin Complex
Wu, G., Xu, G., Schulman, B. A., Jeffrey, P. D., Harper, J. W., & Pavletich, N. P. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00234-x · Cited by 612 · see citing works
Self-citationZhuang, 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) · Molecular Cell · doi:10.1016/j.molcel.2009.09.022 · Cited by 486 · see citing works
Self-citationE3 ubiquitin ligases: styles, structures and functions
Yang, Q., Zhao, J., Chen, D., & Wang, Y. (2021) · Molecular Biomedicine · doi:10.1186/s43556-021-00043-2 · Cited by 435 · see citing works
Drugging the undruggables: exploring the ubiquitin system for drug development
Huang, X., & Dixit, V. M. (2016) · Cell Research · doi:10.1038/cr.2016.31 · Cited by 427 · see citing works
Chan, C.-H., Morrow, J. K., Li, C.-F., Gao, Y., Jin, G., Moten, A., Stagg, L. J., Ladbury, J. E., Cai, Z., Xu, D., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.048 · Cited by 391 · see citing works
Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex
Brzovic, P. S., Keeffe, J. R., Nishikawa, H., Miyamoto, K., Fox, D., Fukuda, M., Ohta, T., & Klevit, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0836054100 · Cited by 346 · see citing works
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Lin, D. I., Barbash, O., Kumar, K. G. S., Weber, J. D., Harper, J. W., Klein-Szanto, A. J. P., Rustgi, A., Fuchs, S. Y., & Diehl, J. A. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.09.007 · Cited by 349 · see citing works
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Lydeard, J. R., Schulman, B. A., & Harper, J. W. (2013) · The EMBO Reports · doi:10.1038/embor.2013.173 · Cited by 327 · see citing works
Self-citationCanettieri, G., Di Marcotullio, L., Greco, A., Coni, S., Antonucci, L., Infante, P., Pietrosanti, L., De Smaele, E., Ferretti, E., Miele, E., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2013 · Cited by 322 · see citing works
Structural basis for Cul3 protein assembly with the BTB-Kelch family of E3 ubiquitin ligases
Canning, P., Cooper, C. D. O., Krojer, T., Murray, J. W., Pike, A. C. W., Chaikuad, A., Keates, T., Thangaratnarajah, C., Hojzan, V., Marsden, B. D., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.437996 · Cited by 284 · see citing works
Nuclear receptors: integration of multiple signalling pathways through phosphorylation
Rochette-Egly, C. (2003) · Cellular Signalling · doi:10.1016/s0898-6568(02)00115-8 · Cited by 291 · see citing works
Linke, K., Mace, P. D., Smith, C. A., Vaux, D. L., Silke, J., & Day, C. L. (2008) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402309 · Cited by 288 · see citing works
Goldenberg, S. J., Cascio, T. C., Shumway, S. D., Garbutt, K. C., Liu, J., Xiong, Y., & Zheng, N. (2004) · Cell · doi:10.1016/j.cell.2004.10.019 · Cited by 280 · see citing works
Self-citationThe statistical mechanics of complex signaling networks: Nerve growth factor signaling.
Brown, K. S., Hill, C. C., Calero, G. A., Myers, C. R., Lee, K. H., Sethna, J. P., & Cerione, R. A. (2004) · Physical Biology · doi:10.1088/1478-3967/1/3/006 · Cited by 265 · see citing works
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Pierce, N. W., Lee, J. E., Liu, X., Sweredoski, M. J., Graham, R. L. J., Larimore, E. A., Rome, M., Zheng, N., Clurman, B. E., Hess, S., et al. (2013) · Cell · doi:10.1016/j.cell.2013.02.024 · Cited by 262 · see citing works
Self-citationDentice, M., Bandyopadhyay, A., Gereben, B., Callebaut, I., Christoffolete, M. A., Kim, B. W., Nissim, S., Mornon, J.-P., Zavacki, A. M., Zeöld, A., et al. (2005) · Nature Cell Biology · doi:10.1038/ncb1272 · Cited by 227 · see citing works
Targeting NEDD8-Activated Cullin-RING Ligases for the Treatment of Cancer
Soucy, T. A., Smith, P. G., & Rolfe, M. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0343 · Cited by 222 · see citing works
Bulatov, E., & Ciulli, A. (2015) · Biochemical Journal · doi:10.1042/bj20141450 · Cited by 237 · see citing works
Two Distinct Types of E3 Ligases Work in Unison to Regulate Substrate Ubiquitylation
Scott, D. C., Rhee, D. Y., Duda, D. M., Kelsall, I. R., Olszewski, J. L., Paulo, J. A., de Jong, A., Ovaa, H., Alpi, A. F., Harper, J. W., et al. (2016) · Cell · doi:10.1016/j.cell.2016.07.027 · Cited by 229 · see citing works
Self-citationStructural assembly of cullin-RING ubiquitin ligase complexes
Zimmerman, E. S., Schulman, B. A., & Zheng, N. (2010) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2010.08.010 · Cited by 227 · see citing works
Self-citationThe NEDD8 Conjugation Pathway and Its Relevance in Cancer Biology and Therapy
Soucy, T. A., Dick, L. R., Smith, P. G., Milhollen, M. A., & Brownell, J. E. (2010) · Genes & Cancer · doi:10.1177/1947601910382898 · Cited by 225 · see citing works
Dynamic Allostery: Linkers Are Not Merely Flexible
Ma, B., Tsai, C.-J., Haliloğlu, T., & Nussinov, R. (2011) · Structure · doi:10.1016/j.str.2011.06.002 · Cited by 222 · see citing works
Tang, X., Orlicky, S., Lin, Z., Willems, A., Neculai, D., Ceccarelli, D., Mercurio, F., Shilton, B. H., Sicheri, F., & Tyers, M. (2007) · Cell · doi:10.1016/j.cell.2007.04.042 · Cited by 209 · see citing works
Cullin–RING ubiquitin E3 ligase regulation by the COP9 signalosome
Cavadini, S., Fischer, E. S., Bunker, R. D., Potenza, A., Lingaraju, G. M., Goldie, K. N., Mohamed, W. I., Faty, M., Petzold, G., Beckwith, R. E. J., et al. (2016) · Nature · doi:10.1038/nature17416 · Cited by 213 · see citing works
Structural regulation of cullin-RING ubiquitin ligase complexes
Duda, D. M., Scott, D. C., Calabrese, M. F., Zimmerman, E. S., Zheng, N., & Schulman, B. A. (2011) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2011.01.003 · Cited by 205 · see citing works
Self-citationPoyurovsky, M. V., Priest, C., Kentsis, A., Borden, K. L., Pan, Z., Pavletich, N., & Prives, C. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601465 · Cited by 203 · see citing works
Structural basis for hijacking CBF-β and CUL5 E3 ligase complex by HIV-1 Vif
Guo, Y., Dong, L., Qiu, X., Wang, Y., Zhang, B., Liu, H., Yu, Y., Zang, Y., Yang, M., & Huang, Z. (2014) · Nature · doi:10.1038/nature12884 · Cited by 202 · see citing works
Scott, D. C., Sviderskiy, V. O., Monda, J. K., Lydeard, J. R., Cho, S. E., Harper, J. W., & Schulman, B. A. (2014) · Cell · doi:10.1016/j.cell.2014.04.037 · Cited by 201 · see citing works
Self-citationUbiquitin ligation to F-box protein targets by SCF–RBR E3–E3 super-assembly
Horn-Ghetko, D., Krist, D. T., Prabu, J. R., Baek, K., Mulder, M. P. C., Klügel, M., Scott, D. C., Ovaa, H., Kleiger, G., & Schulman, B. A. (2021) · Nature · doi:10.1038/s41586-021-03197-9 · Cited by 187 · see citing works
Self-citationAuxin Perception--Structural Insights
Calderon-Villalobos, L. I., Tan, X., Zheng, N., & Estelle, M. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005546 · Cited by 177 · see citing works
Self-citationNEDD8 and ubiquitin ligation by cullin-RING E3 ligases
Baek, K., Scott, D. C., & Schulman, B. A. (2021) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2020.10.007 · Cited by 152 · see citing works
Self-citationA binding motif for Siah ubiquitin ligase
House, C. M., Frew, I. J., Huang, H.-L., Wiche, G., Traficante, N., Nice, E., Catimel, B., & Bowtell, D. D. L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0534783100 · Cited by 148 · see citing works
Targeted disruption of <i>p185/Cul7</i> gene results in abnormal vascular morphogenesis
Arai, T., Kasper, J. S., Skaar, J. R., Ali, S. H., Takahashi, C., & DeCaprio, J. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1733908100 · Cited by 145 · see citing works
A Comprehensive Guide to the MAGE Family of Ubiquitin Ligases
Lee, A. K., & Potts, P. R. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.03.005 · Cited by 136 · see citing works
<i>KCTD</i>: A new gene family involved in neurodevelopmental and neuropsychiatric disorders
Teng, X., Aouacheria, A., Lionnard, L., Metz, K. A., Soane, L., Kamiya, A., & Hardwick, J. M. (2019) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13156 · Cited by 124 · see citing works
Priming and Extending: A UbcH5/Cdc34 E2 Handoff Mechanism for Polyubiquitination on a SCF Substrate
Wu, K., Kovacev, J., & Pan, Z.-Q. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.02.025 · Cited by 126 · see citing works
The SOCS box—Adapting proteins for ubiquitination and proteasomal degradation
Linossi, E. M., & Nicholson, S. E. (2012) · IUBMB Life · doi:10.1002/iub.1011 · Cited by 122 · see citing works
Mayor-Ruiz, C., Jaeger, M. G., Bauer, S., Brand, M., Sin, C., Hanzl, A., Mueller, A. C., Menche, J., & Winter, G. E. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.07.013 · Cited by 119 · see citing works
A conserved mechanism for regulating replisome disassembly in eukaryotes
Jenkyn-Bedford, M., Jones, M. L., Baris, Y., Labib, K. P. M., Cannone, G., Yeeles, J. T. P., & Deegan, T. D. (2021) · Nature · doi:10.1038/s41586-021-04145-3 · Cited by 116 · see citing works
Cand1-Mediated Adaptive Exchange Mechanism Enables Variation in F-Box Protein Expression
Liu, X., Reitsma, J. M., Mamrosh, J. L., Zhang, Y., Straube, R., & Deshaies, R. J. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.01.038 · Cited by 108 · see citing works
Mosadeghi, R., Reichermeier, K. M., Winkler, M., Schreiber, A., Reitsma, J. M., Zhang, Y., Stengel, F., Cao, J., Kim, M., Sweredoski, M. J., et al. (2016) · eLife · doi:10.7554/elife.12102 · Cited by 95 · see citing works
An affinity-directed protein missile system for targeted proteolysis
Fulcher, L. J., Macartney, T., Bozatzi, P., Hornberger, A., Rojas-Fernandez, A., & Sapkota, G. P. (2016) · Open Biology · doi:10.1098/rsob.160255 · Cited by 91 · see citing works
Glenn, K. A., Nelson, R. F., Wen, H. M., Mallinger, A. J., & Paulson, H. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709508200 · Cited by 86 · see citing works
Bai, N., Riching, K. M., Makaju, A., Wu, H., Acker, T. M., Ou, S.-C., Zhang, Y., Shen, X., Bulloch, D. N., Rui, H., et al. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101653 · Cited by 77 · see citing works
Ungermannova, D., Lee, J., Zhang, G., Dallmann, H. G., McHenry, C. S., & Liu, X. (2013) · SLAS Discovery · doi:10.1177/1087057113485789 · Cited by 70 · see citing works
Molecular Architecture of the Ankyrin SOCS Box Family of Cul5-Dependent E3 Ubiquitin Ligases
Muniz, J. R. C., Guo, K., Kershaw, N. J., Ayinampudi, V., von Delft, F., Babon, J. J., & Bullock, A. N. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.06.015 · Cited by 34 · see citing works
Dispersed Sites of HIV Vif-Dependent Polyubiquitination in the DNA Deaminase APOBEC3F
Albin, J. S., Anderson, J. S., Johnson, J. R., Harjes, E., Matsuo, H., Krogan, N. J., & Harris, R. S. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.01.010 · Cited by 25 · see citing works
Kumanomidou, T., Nishio, K., Takagi, K., Nakagawa, T., Suzuki, A., Yamane, T., Tokunaga, F., Iwai, K., Murakami, A., Yoshida, Y., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0140366 · Cited by 21 · see citing works
- Authors
- 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., Conaway, R. C., Conaway, J. W., Harper, J. W., & Pavletich, N. P.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- St. Jude Children's Research Hospital (US)
- Stowers Institute for Medical Research (US)
- Howard Hughes Medical Institute (US)
- NYU Langone Health (US)
- Corresponding author
- Pavletich, Nikola P.
- ORCID
- Venue
- Nature
- Published
- 2002-04
- Volume
- 416
- Issue
- 6882
- Pages
- 703-709
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2121077625
- Cited by
- 1,507
- References
- 50
- Citations by year
- 2026: 41 · 2025: 48 · 2024: 53 · 2023: 52 · 2022: 47 · 2021: 57 · 2020: 55 · 2019: 63 · 2018: 40 · 2017: 54 · 2016: 56 · 2015: 57 · 2014: 62 · 2013: 74 · 2012: 66
- FWCI
- 30.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Leukemia and Lymphoma Society
- National Institutes of Health
- National Institute on Aging (R01AG011085)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Keywords
- SCF ubiquitin ligase, CUL1, RBX1, Skp1, F-box, Skp2, E3 ubiquitin ligase, crystal structure, ring finger, ubiquitination, substrate recognition, scaffold proteins, E2 ubiquitin-conjugating enzyme
- MeSH terms
- NEDD8 Protein, Amino Acid Sequence, Binding Sites, Humans, Ligases, Models, Molecular, Molecular Sequence Data, Peptide Synthases, Protein Binding, Structure-Activity Relationship, Ubiquitins, Sequence Alignment, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Crystallography, X-Ray, Cell Cycle Proteins, Amino Acid Motifs, Protein Structure, Quaternary, Tumor Suppressor Proteins, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, S-Phase Kinase-Associated Proteins, Cullin Proteins, SKP Cullin F-Box Protein Ligases, Macromolecular Substances, Cyclin-Dependent Kinase Inhibitor p27
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