Harnessing the Ubiquitination Machinery to Target the Degradation of Specific Cellular Proteins

A simplified system for generating recombinant adenoviruses

He, T., Zhou, S., da Costa, L. T., Yu, J., Kinzler, K. W., & Vogelstein, B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2509 · Cited by 3,209

The human papilloma virus-16 E7-oncoprotein is able to bind to the retinoblastoma gene product

Dyson, N., Howley, P. M., Münger, K., & Harlow, E. (1989) · Science · doi:10.1126/science.2537532 · Cited by 3,017

UBIQUITIN-DEPENDENT PROTEIN DEGRADATION

Hochstrasser, M. (1996) · Annual Review of Genetics · doi:10.1146/annurev.genet.30.1.405 · Cited by 1,706

SKP1 Connects Cell Cycle Regulators to the Ubiquitin Proteolysis Machinery through a Novel Motif, the F-Box

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

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

Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product.

Münger, K., Werness, B. A., Dyson, N. J., Phelps, W. C., Harlow, E. E., & Howley, P. M. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb08594.x · Cited by 1,204

Regulation of retinoblastoma protein functions by ectopic expression of human cyclins

Hinds, P. W., Mittnacht, S., Dulić, V., Arnold, A., Reed, S. I., & Weinberg, R. A. (1992) · Cell · doi:10.1016/0092-8674(92)90249-c · Cited by 998

A Complex of Cdc4p, Skp1p, and Cdc53p/Cullin Catalyzes Ubiquitination of the Phosphorylated CDK Inhibitor Sic1p

Feldman, R. M. R., Correll, C. C., Kaplan, K. B., & Deshaies, R. J. (1997) · Cell · doi:10.1016/s0092-8674(00)80404-3 · Cited by 820

CDC20 and CDH1 : A Family of Substrate-Specific Activators of APC-Dependent Proteolysis

Visintin, R., Prinz, S., & Amon, A. (1997) · Science · doi:10.1126/science.278.5337.460 · Cited by 812

A Novel Human WD Protein, h-βTrCP, that Interacts with HIV-1 Vpu Connects CD4 to the ER Degradation Pathway through an F-Box Motif

Margottin-Goguet, F., Bour, S. P., Durand, H., Selig, L., Bénichou, S., Richard, V., Thomas, D., Strebel, K., & Bénarous, R. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80056-8 · Cited by 670

Design of Peptide-Based Protein Degraders via Contrastive Deep LearningPreprint

Palepu, K., Ponnapati, M. R., Bhat, S., Tysinger, E., Stan, T., Brixi, G., Koseki, S., & Chatterjee, P. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.23.493169 · Cited by 18

Synthetic biology approaches for targeted protein degradation

Chen, R. P., Gaynor, A. S., & Chen, W. (2019) · Biotechnology Advances · doi:10.1016/j.biotechadv.2019.107446 · Cited by 18

Discovery of X10g as a selective PROTAC degrader of Hsp90α protein for treating breast cancer

Jiang, Q., Fu, M., Tang, Y., Li, G., Tu, G., Wu, X., Wu, Q., Huang, X., Xu, J., Liu, Y., et al. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115690 · Cited by 17

Targeting Degradation of EGFR through the Allosteric Site Leads to Cancer Cell Detachment-Promoted Death

Iradyan, M. A., Iradyan, N., Hulin, P., Hambardzumyan, A. A., Gyulkhandanyan, A., de Sousa, R. A., Hessani, A., Roussakis, C., Bollot, G., Bauvais, C., et al. (2019) · Cancers · doi:10.3390/cancers11081094 · Cited by 17

Proteomic analysis reveals a PLK1-dependent G2/M degradation program and a role for AKAP2 in coordinating the mitotic cytoskeleton

Mouery, R. D., Lukasik, K., Hsu, C., Bonacci, T., Bolhuis, D. L., Wang, X., Mills, C. A., Toomer, E. D., Canterbury, O. G., Robertson, K., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114510 · Cited by 17

The p97-Ufd1-Npl4 ATPase complex ensures robustness of the G2/M checkpoint by facilitating CDC25A degradation

Riemer, A., Dobrynin, G., Dressler, A., Bremer, S., Soni, A., Iliakis, G. E., & Meyer, H. H. (2014) · Cell Cycle · doi:10.4161/cc.27779 · Cited by 17

Targeting protein function: the expanding toolkit for conditional disruption

Campbell, A. E., & Bennett, D. (2016) · Biochemical Journal · doi:10.1042/bcj20160240 · Cited by 16

Targeting protein inactivation through an oligomerization chain reaction

Contegno, F., Cioce, M., Pelicci, P. G., & Minucci, S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.042460299 · Cited by 16

Functionalized Protein Binders in Developmental Biology

Schnider, S. T., Viganò, M., Affolter, M., & Aguilar, G. (2024) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-112122-025214 · Cited by 14

Protein i: interference at protein level by intrabodies

Manikandan, J. (2006) · Frontiers in bioscience · doi:10.2741/2152 · Cited by 15

Intracellular Antibodies for Drug Discovery and as Drugs of the Future

Rabbitts, T. H. (2023) · Antibodies · doi:10.3390/antib12010024 · Cited by 16

Development of a targeted BioPROTAC degrader selective for misfolded SOD1

Chisholm, C. G., Bartlett, R., Brown, M. L., Proctor, E., Farrawell, N. E., Gorman, J., Delerue, F., Ittner, L. M., Vine, K. L., Ecroyd, H. W., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65481-w · Cited by 15

Frontiers of protein expression control with conditional degrons

Kanemaki, M. T. (2012) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-012-1203-y · Cited by 14

Engineering a single ubiquitin ligase for the selective degradation of all activated ErbB receptor tyrosine kinases

Kong, F., Zhang, J., Li, Y., Hao, X., Ren, X., Li, H., & Zhou, P. (2013) · Oncogene · doi:10.1038/onc.2013.33 · Cited by 13

A Method for Conditional Regulation of Protein Stability in Native or Near-Native Form

Miyamae, Y., Chen, L., Utsugi, Y., Farrants, H., & Wandless, T. J. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.09.004 · Cited by 13

Targeting protein ubiquitination for drug discovery. What is in the drug discovery toolbox?

Swinney, D. C. (2001) · Drug Discovery Today · doi:10.1016/s1359-6446(00)01650-0 · Cited by 13

Targeting UBE2C for degradation by bioPROTACs based on bacterial E3 ligase

Wang, J., Zhang, M., Liu, S., He, Z., Wang, R. Y., Liang, M., An, Y., Jiang, C., Song, C., Ning, Z., et al. (2022) · Chinese Chemical Letters · doi:10.1016/j.cclet.2022.08.012 · Cited by 11

Steuerung der intrazellulären Proteinmenge durch niedermolekulare Modulatoren des Ubiquitin‐Proteasom‐Systems

Buckley, D. L., & Crews, C. M. (2014) · Angewandte Chemie · doi:10.1002/ange.201307761 · Cited by 11

Proteolysis targeting peptide (PROTAP) strategy for protein ubiquitination and degradation

Zheng, J., Tan, C., Xue, P., Cao, J., Liu, F., Tan, Y. C., & Jiang, Y. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.01.158 · Cited by 11

Development of AlissAID system targeting GFP or mCherry fusion protein

Ogawa, Y., Nishimura, K., Obara, K., & Kamura, T. (2023) · PLoS Genetics · doi:10.1371/journal.pgen.1010731 · Cited by 9

Redirecting the specificity of tripartite motif containing-21 scaffolds using a novel discovery and design approach

VanDyke, D., Xu, L., Sargunas, P. R., Gilbreth, R. N., Baca, M., Gao, C., Hunt, J., & Spangler, J. B. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105381 · Cited by 10

Targeted protein and protein-condensate degradation in plant science research and crop breeding

Niu, R., Luo, M., Wen, Q., Xiong, Y., Dang, H., & Xu, G. (2025) · Molecular Plant · doi:10.1016/j.molp.2025.06.013 · Cited by 10

Pac-Man for biotechnology: co-opting degrons for targeted protein degradation to control and alter cell function

Yu, G., Rosenberg, J. N., Betenbaugh, M. J., & Oyler, G. A. (2015) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2015.08.023 · Cited by 10

Antitumor effect of F-PBFβ-TrCP-induced targeted PTTG1 degradation in HeLa cells

Mo, Z., Zu, X., Xie, Z., Li, W., Ning, H., Jiang, Y., & Xu, W. F. (2008) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2008.09.004 · Cited by 10

Targeted substrate degradation by an engineered double RING ubiquitin ligase

Oyake, D., Nishikawa, H., Koizuka, I., Fukuda, M., & Ohta, T. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00673-3 · Cited by 10

Reference Systems for Kinase Drug Discovery: Chemical Genetic Approaches to Cell-Based Assays

Whitney, J. A. (2004) · Assay and Drug Development Technologies · doi:10.1089/1540658041850625 · Cited by 9

Engineering New Protein–Protein Interactions on the β‐Propeller Fold by Yeast Cell Surface Display

Zhang, K., Li, H., Bhuripanyo, K., Zhao, B., Chen, T. F., Zheng, N., & Yin, J. (2013) · ChemBioChem · doi:10.1002/cbic.201200718 · Cited by 8

The ends and means of artificially induced targeted protein degradation

Prabha, C. R., Mukherjee, S., Raman, R., & Kulkarni, S. (2012) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-012-4471-8 · Cited by 8

Inducible Degron and Its Application to Creating Conditional Mutants

Dohmen, R. J. (2005) · Humana Press eBooks · doi:10.1385/1-59259-958-3:145 · Cited by 8

Botulinum neurotoxin: Progress in negating its neurotoxicity; and in extending its therapeutic utility via molecular engineering. MiniReview

Kostrzewa, R. M., Kostrzewa, J. P., & Kostrzewa, J. P. (2015) · Peptides · doi:10.1016/j.peptides.2015.07.003 · Cited by 6

Adapter-mediated Substrate Selection for Endoplasmic Reticulum-associated Degradation

Corcoran, K., Wang, X., & Lybarger, L. P. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808258200 · Cited by 6

Ion channel inhibition by targeted recruitment of NEDD4-2 with divalent nanobodies

Darko-Boateng, A., Afriyie, E., Morgenstern, T. J., Shanmugam, S. K., Zou, X., Laloudakis, Y. D., Choudhury, P., Desai, M., Kass, R. S., Vallese, F., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-67068-x · Cited by 8

To homeostasis and beyond! Recent advances in the medicinal chemistry of heterobifunctional derivatives

Castagna, D., Gourdet, B., Hjerpe, R., MacFaul, P., Novak, A., Révol, G., Rochette, É., & Jordan, A. M. (2024) · Progress in medicinal chemistry · doi:10.1016/bs.pmch.2024.07.002 · Cited by 5

Expression of scfv antibodies in xenopus embryos to disrupt protein function: Implications for large‐scale evaluation of the embryonic proteome

Abler, L. L., & Sheets, M. D. (2003) · genesis · doi:10.1002/gene.10171 · Cited by 5

Maximizing target protein ablation by integration of RNAi and protein knockout

Hannah, J., & Zhou, P. (2011) · Cell Research · doi:10.1038/cr.2011.89 · Cited by 5

Protein silencing with Phylomers: a new tool for target validation and generating lead biologicals targeting protein interactions

Watt, P. M., Heinrich, T. K., & Thomas, W. R. (2006) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.1.5.491 · Cited by 5

A small-molecule SMASh hit

Hannah, J., & Zhou, P. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1886 · Cited by 4

Ectopic Targeting of Substrates to the Ubiquitin Pathway

Zhang, J., & Zhou, P. (2005) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(05)99053-8 · Cited by 4

A High-Throughput Cell-Based Screen Identified a 2-[(E)-2-Phenylvinyl]-8-Quinolinol Core Structure That Activates p53

Bechill, J., Zhong, R., Zhang, C., Solomaha, E., & Spiotto, M. T. (2016) · PLoS ONE · doi:10.1371/journal.pone.0154125 · Cited by 4

Novel methods for studying multiprotein complexes in vivo

Mehta, V., & Trinkle‐Mulcahy, L. (2013) · F1000Prime Reports · doi:10.12703/p5-30 · Cited by 4

Potential applications of intracellular antibodies (intrabodies) in stem cell therapeutics

Heng, B. C., Kemeny, D. M., Liu, H., & Cao, T. (2005) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2005.tb00348.x · Cited by 4

Protein engineering strategies with potential applications for altering clinically relevant cellular pathways at the protein level

Regan, L., Hinrichsen, M. R., & Oi, C. (2016) · Expert Review of Proteomics · doi:10.1586/14789450.2016.1172966 · Cited by 3

Mechanism of Action of Botulinum Neurotoxin and Overview of Medical Countermeasures for Intoxication

Lukey, B. J., Romano, J. A., Jr., Romano, J. A., Salem, H., Lukey, B. J., & Salem, H. (2007) · CRC Press eBooks · doi:10.1201/9781420046625-22 · Cited by 3

Proteome editing using engineered proteins that hijack cellular quality control machinery

Lopez‐Barbosa, N., Ludwicki, M. B., & DeLisa, M. P. (2019) · AIChE Journal · doi:10.1002/aic.16854 · Cited by 2

Degron Tagging Using mAID and SMASh Tags in RPE-1 Cells

Crncec, A., & Hochegger, H. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-1904-9_14 · Cited by 2

7 Putting genetics into optogenetics: knocking out proteins with light

LaBella, M. L., Sigrist, S. J., & Jørgensen, E. M. (2013) · De Gruyter eBooks · doi:10.1515/9783110270723.79 · Cited by 1

Molecular Basis for Persistence of Botulinum Neurotoxin: The Role of Intracellular Protein Degradation Pathways

Tsai, Y. C., Moller, B. E., Adler, M., & Oyler, G. A. (2014) · Springer eBooks · doi:10.1007/978-1-4614-9454-6_9 · Cited by 1

Commentary: Intracellular antibodies (intrabodies) versus RNA interference for therapeutic applications

Cao, T., & Heng, B. C. (2005) · National University of Singapore · Cited by 1

Targeted Protein Degradation – The Story So Far

O’Donovan, D. H., Luh, L. M., & Cromm, P. M. (2022) · Wiley eBooks · doi:10.1002/9783527836208.ch1 · Cited by 1

Proteomic Analysis Reveals a PLK1-Dependent G2/M Degradation Program and Links PKA-AKAP2 to Cell Cycle ControlPreprint

Mouery, R. D., Hsu, C., Bonacci, T., Bolhuis, D. L., Wang, X., Mills, C. A., Toomer, E. D., Canterbury, O. G., Robertson, K., Branigan, T. B., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.11.561963 · Cited by 1

EVIDENCE FOR ADAPTER-MEDIATED SUBSTRATE SELECTION IN ENDOPLASMIC RETICULUM ASSOCIATED DEGRADATION

Corcoran, K. (2009) · UA Campus Repository (The University of Arizona)

The role of the ubiquitin-proteasome system in neurodegenerative disorders

Verhoef, L. G. G. C. (2006) · Figshare

The 20S Proteasome from Thermoplasma acidophilum

Nazario, J. O. (2002)

Recombinant intracellular antibodies for molecular gene therapy of HIV-1 infection

da Silva, F. N. C. A. (2008)

Targeted Intracellular Protein Degradation as a Potential Therapeutic Strategy

Schneekloth, A. R., & Crews, C. M. (2010) · Royal Society of Chemistry eBooks · doi:10.1039/9781849732178-00064

Recombinant Intracellular Antibodies For Molecular Gene Therapy of HIV-1 Infection

Farmácia, F. D. (2008)

β-TrCP-mediated ubiquitination and degradation of liver-enriched transcription factor CREB-H

Cheng, Y. (2016) · The HKU Scholars Hub (University of Hong Kong) · doi:10.5353/th_b5816255

Mechanism of Action of Botulinum Neurotoxin and Overview of Medical Countermeasures for Intoxication

Adler, M., Anderson, J. B., Deshpande, S. S., Lebeda, F. J., Millard, C. B., Oyler, G. A., Apland, J. P., & Nicholson, J. D. (2007) · CRC Press eBooks · doi:10.1201/9781420046625.ch16

Genetically-encoded degraders as versatile modulators of intracellular therapeutic targets

Dai, C., Wang, J., Tu, L., Pan, Z., Yang, J., Zhou, S. Y., Luo, Q., Zhu, L., & Ye, Y. (2023) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2023.100458 · Cited by 1

Targeted Protein Degradation Technology: A Novel Strategy for Cancer Therapy

Xu, A., & Reynolds, E. (2024) · Journal of Student Research · doi:10.47611/jsrhs.v13i1.6455

Proteolysis Targeting Chimera (PROTACs): An Attractive Technology in CVD Therapeutics—Opportunities and Challenges

Gupta, D., Khedpande, N., & Barve, K. H. (2024) · Springer eBooks · doi:10.1007/978-981-97-5077-1_16

From inhibition to degradation: Cutting-edge technology in COVID-19 drug discovery

Adediran, E. O., Ikhoyameh, M., & Gbadebo, O. S. (2025) · Annales Pharmaceutiques Françaises · doi:10.1016/j.pharma.2025.08.002

Breaking the proteasome balance: α-synuclein and the ubiquitin-proteasome system

Ali, T. T., Popova, B., & Braus, G. H. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1906331

BindingDB Entry 50022364: Discovery of X10g as a selective PROTAC degrader of Hsp90α protein for treating breast cancer.

BindingDB (2025) · UC San Diego · doi:10.7270/q2zg6z00

Targeted protein degradation

Zhou, P. (2004) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2004.10.012 · Cited by 50

Ectopic Targeting of Substrates to the Ubiquitin Pathway

Zhang, J., & Zhou, P. (2005) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(05)99053-8 · Cited by 4

Ubiquibodies, Synthetic E3 Ubiquitin Ligases Endowed with Unnatural Substrate Specificity for Targeted Protein Silencing

Portnoff, A. D., Stephens, E. A., Varner, J. D., & DeLisa, M. P. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.544825 · Cited by 83

Ubiquibodies: Engineered Ubiquitin Ligases With Unnatural Substrate Specificity For Targeted Protein Silencing

Portnoff, A. D. (2014) · eCommons (Cornell University)

[Utilization of targeting specific proteins for ubiquitination and degradation].

Ma, Y., Zhang, Q., & Chen, J. (2010) · PubMed · doi:10.3881/j.issn.1000-503x.2010.01.029