Cited by 173Protein Degradation and InhibitorsUbiquitin and proteasome pathwaysChemical Synthesis and Analysis

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bioPROTACs as versatile modulators of intracellular therapeutic targets including proliferating cell nuclear antigen (PCNA)

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Lim, Shuhui, Khoo, Regina, Peh, Khong Ming, Teo, Jinkai, Chang, Shih Chieh, Ng, Simon, Beilhartz, Greg L., Melnyk, Roman A., Johannes, Charles W., Brown, Christopher J., Lane, David P., Henry, Brian, Partridge, Anthony W.·2020·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1920251117PMC PMC7084165

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Abstract

Significance: Intracellular proteins interact with each other to perform functions that are critical to normal and disease states. Attempts at altering pathological protein–protein interactions with traditional approaches have largely failed. Here, we explore an emerging approach we call “bioPROTACs”—engineered fusion proteins that consist of a target binding domain and an E3 ligase, an arrangement that results in the specific degradation of the therapeutic target. Our systematic study shows bioPROTAC design requirements are highly flexible in terms of both the binding domain and E3 ligase components. Resulting molecules can be used as powerful tools for uncovering biology, informing on the design of small molecule target degraders (e.g. PROTACs), and, if delivery issues can be addressed, potential therapeutics.

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Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566
PCNA, the Maestro of the Replication Fork
Moldovan, G.-L., Pfander, B., & Jentsch, S. (2007) · Cell · doi:10.1016/j.cell.2007.05.003 · Cited by 1,796
Induced protein degradation: an emerging drug discovery paradigm
Lai, A. C., & Crews, C. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.211 · Cited by 1,486
Structural basis of PROTAC cooperative recognition for selective protein degradation
Gadd, M. S., Testa, A., Lucas, X., Chan, K.-H., Chen, W., Lamont, D. J., Zengerle, M., & Ciulli, A. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2329 · Cited by 1,242
Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery
Kowalski, P. S., Rudra, A., Miao, L., & Anderson, D. G. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.02.012 · Cited by 1,127
The dTAG system for immediate and target-specific protein degradation
Nabet, B., Roberts, J. M., Buckley, D. L., Paulk, J., Dastjerdi, S., Yang, A., Leggett, A. L., Erb, M. A., Lawlor, M. A., Souza, A., et al. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0021-8 · Cited by 1,118
Lessons in PROTAC Design from Selective Degradation with a Promiscuous Warhead
Bondeson, D. P., Smith, B. E., Burslem, G. M., Buhimschi, A. D., Hines, J., Jaime-Figueroa, S., Wang, J., Hamman, B. D., Ishchenko, A., & Crews, C. M. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.09.010 · Cited by 923
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Rothbauer, U., Zolghadr, K., Tillib, S. V., Nowak, D., Schermelleh, L., Gahl, A., Backmann, N., Conrath, K., Muyldermans, S., Cardoso, M. C., et al. (2006) · Nature Methods · doi:10.1038/nmeth953 · Cited by 715
The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study
Burslem, G. M., Smith, B. E., Lai, A. C., Jaime-Figueroa, S., McQuaid, D. C., Bondeson, D. P., Toure, M., Dong, H., Qian, Y., Wang, J., et al. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.09.009 · Cited by 686
Small‐Molecule PROTACS: New Approaches to Protein Degradation
Toure, M., & Crews, C. M. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201507978 · Cited by 674

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“100 The second domain typically consists of an E3 ubiquitin ligase, which adds ubiquitin to the target protein, marking it for degradation 97 (Fig.”
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Self-citation
The E3 ubiquitin ligase Cul5 regulates hematopoietic stem cell function for steady-state hematopoiesis in mice
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Engineering a U-box of E3 ligase E4B through yeast surface display-based functional screening generates a variant with enhanced ubiquitin ligase activity
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Authors: Lim, S., Khoo, R., Peh, K. M., Teo, J., Chang, S. C., Ng, S., Beilhartz, G. L., Melnyk, R. A., Johannes, C. W., Brown, C. J., Lane, D. P., Henry, B., & Partridge, A. W.
Affiliations: MSD (Singapore) (SG)
Pacific Translational Biomarkers, MSD International, Singapore 138665;
Hospital for Sick Children (CA)
University of Toronto (CA)
Agency for Science, Technology and Research (SG)
Corresponding author: Partridge, Anthony W.
ORCID: Peh, Khong Ming
Ng, Simon
Beilhartz, Greg L.
Melnyk, Roman A.
Johannes, Charles W.
Brown, Christopher J.
Lane, David P.
Henry, Brian
Partridge, Anthony W.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2020-03-02
Volume: 117
Issue: 11
Pages: 5791-5800
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1920251117
PMC: PMC7084165
OpenAlex: W3010201122
Cited by: 170
References: 52
Citations by year: 2026: 30 · 2025: 38 · 2024: 35 · 2023: 26 · 2022: 18 · 2021: 15 · 2020: 8
FWCI: 5.43
Type: journal article
Language: en
Open access: green
doi.org
Licence: www.pnas.org/site/aboutpnas/licenses.xhtml (vor, 184 d)
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
Keywords: PROTACs, targeted protein degradation, proliferating cell nuclear antigen, DNA synthesis, cell cycle progression, oncology drug targets
MeSH terms: Binding Sites, Humans, Protein Binding, Recombinant Proteins, Protein Engineering, Proliferating Cell Nuclear Antigen, Ubiquitin-Protein Ligases, HEK293 Cells, Molecular Targeted Therapy, Proteolysis

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bioPROTACs as versatile modulators of intracellular therapeutic targets including proliferating cell nuclear antigen (PCNA)

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