The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Tunable and reversible drug control of protein production via a self-excising degron
Open accessAbstract
An effective method for direct chemical control over the production of specific proteins would be widely useful. We describe small molecule-assisted shutoff (SMASh), a technique in which proteins are fused to a degron that removes itself in the absence of drug, resulting in the production of an untagged protein. Clinically tested HCV protease inhibitors can then block degron removal, inducing rapid degradation of subsequently synthesized copies of the protein. SMASh allows reversible and dose-dependent shutoff of various proteins in multiple mammalian cell types and in yeast. We also used SMASh to confer drug responsiveness onto an RNA virus for which no licensed inhibitors exist. As SMASh does not require the permanent fusion of a large domain, it should be useful when control over protein production with minimal structural modification is desired. Furthermore, as SMASh involves only a single genetic modification and does not rely on modulating protein-protein interactions, it should be easy to generalize to multiple biological contexts.
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“Accordingly, AP1867-derivative PROTACs can mediate the selective degradation of heterologous FKBP12F36V-tagged proteins, enforcing rapid and potent depletion in vitro and in vivo200,201.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [200]
In the citing paper
“In addition, Nabet and colleagues200,201 have developed the dTag system that uses PROTACs composed of a CRBN or VHL ligand, a linker and an AP1867 derivative.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [200]
In the citing paper
“Fusion of a SMASh-tag to either terminus of target proteins exhibits a degron-like function, and protein stability is tuneable with asunaprevir doses ranging from 0.15 nM (slightly reduced levels) to 1.5 µM (undetectable).”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [34]
In the citing paper
“No adverse effects on cell growth induced by asunaprevir were reported [34].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [34]
In the citing paper
“Fused to either the N- or C-terminus of a POI, and connected by an NS3 cleavage site, the degron continuously removes itself from the fusion protein, leaving the POI untagged within the cell (Fig. 2c).”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [34]
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Citations
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Metadata
- Authors
- Chung, H. K., Jacobs, C. L., Huo, Y., Yang, J., Krumm, S. A., Plemper, R. K., Tsien, R. Y., & Lin, M. Z.
- Affiliations
- Stanford University (US)
- Stanford Medicine (US)
- University of California San Diego (US)
- Emory University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Lin, Michael Z
- Venue
- Nature Chemical Biology
- Published
- 2015-07-27
- Volume
- 11
- Issue
- 9
- Pages
- 713-720
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC4543534
- OpenAlex
- W1043004949
- Cited by
- 233
- References
- 56
- Citations by year
- 2026: 21 · 2025: 21 · 2024: 25 · 2023: 23 · 2022: 24 · 2021: 26 · 2020: 30 · 2019: 25 · 2018: 18 · 2017: 10 · 2016: 6 · 2015: 3
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM098734, P50GM107615)
- National Institute of Allergy and Infectious Diseases (R01AI071002, R01AI083402, R21AI119196)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD079327)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Keywords
- smash, protein degradation, HCV protease inhibitors, RNA viruses, yeast, mammalian cells
- MeSH terms
- Viral Proteases, Amino Acid Sequence, Animals, Bacterial Proteins, Binding Sites, Carrier Proteins, Chlorocebus aethiops, Gene Expression Regulation, HeLa Cells, Humans, Isoquinolines, Luminescent Proteins, Molecular Sequence Data, Neurons, Protease Inhibitors, Protein Binding, Recombinant Fusion Proteins, Serine Endopeptidases, Sulfonamides, Vero Cells, Hepacivirus, Rats, Sprague-Dawley, Viral Nonstructural Proteins, Nucleoside-Triphosphatase, Intracellular Signaling Peptides and Proteins, Rats, DEAD-box RNA Helicases, HEK293 Cells, Proteolysis, Primary Cell Culture
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