Ubiquitin: structures, functions, mechanisms

Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O 2 -Regulated Prolyl Hydroxylation

Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535

HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing

Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · cited 10×

In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2

Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., et al. (2004) · Science · doi:10.1126/science.1092472 · Cited by 4,661

Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain

Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J., & Pavletich, N. P. (1996) · Science · doi:10.1126/science.274.5289.948 · Cited by 2,206

A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein

Chau, V., Tobias, J. W., Bachmair, A., Marriott, D., Ecker, D. J., Gonda, D. K., & Varshavsky, A. (1989) · Science · doi:10.1126/science.2538923 · Cited by 1,535

Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex

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) · Nature · doi:10.1038/416703a · Cited by 1,507

RING Finger Proteins

Joazeiro, C. A. P., & Weissman, A. M. (2000) · Cell · doi:10.1016/s0092-8674(00)00077-5 · Cited by 1,249

Molecular dissection of autophagy: two ubiquitin-like systems

Ohsumi, Y. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056522 · Cited by 1,240 · cited 2×

Interaction of the Fanconi Anemia Proteins and BRCA1 in a Common Pathway

Garcia-Higuera, I., Taniguchi, T., Ganesan, S., Meyn, M. S., Timmers, C., Hejna, J., Grompe, M., & D'Andrea, A. D. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00173-3 · Cited by 1,198

Independent function of two destruction domains in hypoxia-inducible factor-α chains activated by prolyl hydroxylation

Masson, N., Willam, C., Maxwell, P. H., Pugh, C. W., & Ratcliffe, P. J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.18.5197 · Cited by 1,014 · cited 10×

A genomic and functional inventory of deubiquitinating enzymes.

Nijman, S. M. B., Luna-Vargas, M. P. A., Velds, A., Brummelkamp, T. R., Dirac, A. M. G., Sixma, T. K., & Bernards, R. (2005) · Cell · doi:10.1016/j.cell.2005.11.007 · Cited by 1,854

Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes.

Reyes-Turcu, F. E., Ventii, K. H., & Wilkinson, K. D. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.082307.091526 · Cited by 1,396

Proteasome-Independent Functions of Ubiquitin in Endocytosis and Signaling

Mukhopadhyay, D., & Riezman, H. (2007) · Science · doi:10.1126/science.1127085 · Cited by 1,221

Structural insights into the catalysis and regulation of E3 ubiquitin ligases

Buetow, L., & Huang, D. T. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.91 · Cited by 679

Autoregulation of Parkin activity through its ubiquitin‐like domain

Chaugule, V. K., Burchell, L., Barber, K. R., Sidhu, A., Leslie, S. J., Shaw, G. S., & Walden, H. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.204 · Cited by 339

BIRC7–E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer

Dou, H., Buetow, L., Sibbet, G. J., Cameron, K., & Huang, D. T. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2379 · Cited by 319

Endocytosis: the DUB version

Clague, M. J., & Urbé, S. (2006) · Trends in Cell Biology · doi:10.1016/j.tcb.2006.09.002 · Cited by 244

p53 regulation by ubiquitin

Brooks, C. L., & Gu, W. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.05.022 · Cited by 186

Activity-enhancing mutations in an E3 ubiquitin ligase identified by high-throughput mutagenesis

Starita, L. M., Pruneda, J. N., Lo, R. S., Fowler, D. M., Kim, H. J., Hiatt, J. B., Shendure, J., Brzovic, P. S., Fields, S., & Klevit, R. E. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303309110 · Cited by 183

Inactivation of HAUSP in vivo modulates p53 function.

Kon, N., Kobayashi, Y., Li, M., Brooks, C. L., Ludwig, T., & Gu, W. (2010) · Oncogene · doi:10.1038/onc.2009.427 · Cited by 176

Genetic epidemiology of amyotrophic lateral sclerosis

Majoor‐Krakauer, D., Willems, P., & Hofman, A. (2003) · Clinical Genetics · doi:10.1046/j.0009-9163.2002.00001.x · Cited by 147

Leptin Administration Favors Muscle Mass Accretion by Decreasing FoxO3a and Increasing PGC-1α in ob/ob Mice

Sáinz, N., Rodríguez, A., Catalán, V., Becerril, S., Ramírez, B., Gómez-Ambrosi, J., & Frühbeck, G. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006808 · Cited by 135

The Proteasome in Modern Drug Discovery: Second Life of a Highly Valuable Drug Target

Cromm, P. M., & Crews, C. M. (2017) · ACS Central Science · doi:10.1021/acscentsci.7b00252 · Cited by 136

HECT E3 ubiquitin ligases – emerging insights into their biological roles and disease relevance

Wang, Y., Argiles-Castillo, D., Kane, E. I., Zhou, A., & Spratt, D. E. (2020) · Journal of Cell Science · doi:10.1242/jcs.228072 · Cited by 128

USP7 Is a Master Regulator of Genome Stability

Valles, G. J., Bezsonova, I., Woodgate, R., & Ashton, N. W. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00717 · Cited by 114

Degradation of Postsynaptic Scaffold GKAP and Regulation of Dendritic Spine Morphology by the TRIM3 Ubiquitin Ligase in Rat Hippocampal Neurons

Hung, A. Y., Sung, C. C., Brito, I. L., & Sheng, M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009842 · Cited by 106

Histone methylation and ubiquitination with their cross-talk and roles in gene expression and stability

Shukla, A., Chaurasia, P., & Bhaumik, S. R. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8605-1 · Cited by 98

Linear ubiquitination at a glance

Spit, M., Rieser, E., & Walczak, H. (2019) · Journal of Cell Science · doi:10.1242/jcs.208512 · Cited by 94

Advances in targeted degradation of endogenous proteins

Röth, S., Fulcher, L. J., & Sapkota, G. P. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03112-6 · Cited by 92

A new mechanism of RhoA ubiquitination and degradation: Roles of SCF(FBXL19) E3 ligase and Erk2

Wei, J., Mialki, R. K., Dong, S., Khoo, A., Mallampalli, R. K., Zhao, Y., & Zhao, J. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.07.005 · Cited by 92

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

Catalysis of Lysine 48-Specific Ubiquitin Chain Assembly by Residues in E2 and Ubiquitin

Rodrigo-Brenni, M. C., Foster, S. A., & Morgan, D. O. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.07.027 · Cited by 91

Targeting endogenous proteins for degradation through the affinity-directed protein missile system

Fulcher, L. J., Hutchinson, L. D., Macartney, T. J., Turnbull, C., & Sapkota, G. P. (2017) · Open Biology · doi:10.1098/rsob.170066 · Cited by 79

Ataxin-3 Deubiquitination Is Coupled to Parkin Ubiquitination via E2 Ubiquitin-conjugating Enzyme

Durcan, T. M., Kontogiannea, M., Bedard, N., Wing, S. S., & Fon, E. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.288449 · Cited by 79

Regulation of TGF-β Superfamily Signaling by SMAD Mono-Ubiquitination

Xie, F., Zhang, Z., Van Dam, H., Zhang, L., & Zhou, F. (2014) · Cells · doi:10.3390/cells3040981 · Cited by 70

Modeling Late-Onset Sporadic Alzheimer’s Disease through BMI1 Deficiency

Flamier, A., El Hajjar, J., Adjaye, J., Fernandes, K. J., Abdouh, M., & Bernier, G. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.097 · Cited by 65

The Yeast Ubr1 Ubiquitin Ligase Participates in a Prominent Pathway That Targets Cytosolic Thermosensitive Mutants for Degradation

Khosrow-Khavar, F., Fang, N. N., Ng, A. H. M., Winget, J. M., Comyn, S. A., & Mayor, T. (2012) · G3 Genes|Genomes|Genetics · doi:10.1534/g3.111.001933 · Cited by 42

Genome-Wide Analysis Identifies MYND-Domain Protein Mub1 as an Essential Factor for Rpn4 Ubiquitylation

Ju, D., Wang, X., Xu, H., & Xie, Y. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01787-07 · Cited by 38

Shigella effector IpaH1.4 subverts host E3 ligase RNF213 to evade antibacterial immunity

Zhou, X., Zhang, H., Wang, Y., Wang, D., Lin, Z., Zhang, Y., Tang, Y., Liu, J., Yao, Y.-F., Zhang, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58432-y · Cited by 17

Structural Dynamics of E6AP E3 Ligase HECT Domain and Involvement of a Flexible Hinge Loop in the Ubiquitin Chain Synthesis Mechanism

Takeda, K., Flechsig, H., Muro, I., Amyot, R., Kobayashi, F., Kodera, N., Ando, T., & Konno, H. (2023) · Nano Letters · doi:10.1021/acs.nanolett.3c04150 · Cited by 13

KPNA2 Silencing, Regulated by E3 Ubiquitin Ligase FBXW7, Alleviates Endothelial Dysfunction and Inflammation Through Inhibiting the Nuclear Translocation of p65 and IRF3: A Possible Therapeutic Approach for Atherosclerosis

Xing, Z., Zhen, Y., Chen, J., Du, M., Li, D., Liu, R., & Zheng, J. (2023) · Inflammation · doi:10.1007/s10753-023-01863-w · Cited by 12

Redox control of the deubiquitinating enzyme Ubp2 regulates translation during stress

Santos, C. M., Cizubu, B. K., Okonkwo, D. A., Chen, C.-Y., Maske, N., Snyder, N. A., Simões, V., Washington, E. J., & Silva, G. M. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107870 · Cited by 5

Scalable insect cell expression and purification screening applied to CRL4-DCAF substrate receptors

(2026) · doi:10.1016/j.pep.2026.106907