Correcting temperature-sensitive protein folding defects
Open accessAbstract
Recently, we found that different low molecular weight compounds, all known to stabilize proteins in their native conformation, are effective in correcting the temperature-sensitive protein folding defect associated with the deltaF508 cystic fibrosis transmembrane regulator (CFTR) protein. Here we examined whether the folding of other proteins which exhibit temperature-sensitive folding defects also could be corrected via a similar strategy. Cell lines expressing temperature-sensitive mutants of the tumor suppressor protein p53, the viral oncogene protein pp60src, or a ubiquitin activating enzyme E1, were incubated at the nonpermissive temperature (39.5 degrees C) in the presence of glycerol, trimethylamine N-oxide or deuterated water. In each case, the cells exhibited phenotypes similar to those observed when the cells were incubated at the permissive temperature (32.5 degrees C), indicative that the particular protein folding defect had been corrected. These observations, coupled with our earlier work and much older studies in yeast and bacteria, indicate that protein stabilizing agents are effective in vivo for correcting protein folding abnormalities. We suggest that this type of approach may prove to be useful for correcting certain protein folding abnormalities associated with human diseases.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
TMAO has both hydrophobic and hydrophilic properties and can alter protein conformation and stability.
“TMAO is rather unique and possesses both hydrophobic and hydrophilic properties and the known ability to alter protein confirmation and stability”
From Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk (2016) · cites this paper as Brown et al., 1997
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Living with Water Stress: Evolution of Osmolyte Systems
Yancey, P. H., Clark, M. E., Hand, S. C., Bowlus, R. D., & Somero, G. N. (1982) · Science · doi:10.1126/science.7112124 · Cited by 3,724 · see citing works
Cheng, S. H., Gregory, R. J., Marshall, J., Paul, S., Souza, D. W., White, G. A., O’Riordan, C. R., & Smith, A. E. (1990) · Cell · doi:10.1016/0092-8674(90)90148-8 · Cited by 1,792 · see citing works
Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive
Denning, G. M., Anderson, M. P., Amara, J. F., Marshall, J., Smith, A. E., & Welsh, M. J. (1992) · Nature · doi:10.1038/358761a0 · Cited by 1,236 · see citing works
Mechanism of protein stabilization by glycerol: preferential hydration in glycerol-water mixtures
Gekko, K., & Timasheff, S. N. (1981) · Biochemistry · doi:10.1021/bi00519a023 · Cited by 1,189 · see citing works
Finlay, C. A., Hinds, P. W., Tan, T., Eliyahu, D., Oren, M., & Levine, A. J. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.2.531 · Cited by 1,144 · see citing works
Michalovitz, D., Halevy, O., & Oren, M. (1990) · Cell · doi:10.1016/0092-8674(90)90113-s · Cited by 769 · see citing works
Increased thermal stability of proteins in the presence of sugars and polyols
Back, J. F., OAKENFULL, D. G., & Smith, M. B. (1979) · Biochemistry · doi:10.1021/bi00590a025 · Cited by 760 · see citing works
Defective protein folding as a basis of human disease
Thomas, P., Qu, B.-H., & Pedersen, P. L. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89100-8 · Cited by 531 · see citing works
Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein.Preprint
Martinez, J., Georgoff, I., Martinez, J., & Levine, A. J. (1991) · Genes & Development · doi:10.1101/gad.5.2.151 · Cited by 528 · see citing works
Glycerol Reverses the Misfolding Phenotype of the Most Common Cystic Fibrosis Mutation
Sato, S., Ward, C. L., Krouse, M. E., Wine, J. J., & Kopito, R. R. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.2.635 · Cited by 519 · see citing works
Chloride Conductance Expressed by ΔF508 and Other Mutant CFTRs In Xenopus Oocytes
Drumm, M. L., Wilkinson, D. J., Smit, L. S., Worrell, R. T., Strong, T. V., Frizzell, R. A., Dawson, D. C., & Collins, F. S. (1991) · Science · doi:10.1126/science.1722350 · Cited by 496 · see citing works
Thermodynamic and kinetic examination of protein stabilization by glycerol
Gekko, K., & Timasheff, S. N. (1981) · Biochemistry · doi:10.1021/bi00519a024 · Cited by 482 · see citing works
Increased thermal stability of proteins in the presence of naturally occurring osmolytes
Santoro, M. M., Liu, Y., Khan, S. M. A., Hou, L. X., & Bolen, D. W. (1992) · Biochemistry · doi:10.1021/bi00138a006 · Cited by 434 · see citing works
Lin, T.-Y., & Timasheff, S. N. (1994) · Biochemistry · doi:10.1021/bi00208a021 · Cited by 371 · cited 1× · see citing works
“We refer the reader to some excellent review articles which discuss in more detail the effects of these different compounds on protein folding and stability (25, 30, 31).”
BackgroundMolecular basis of osmotic regulation
Burg, M. B. (1995) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1995.268.6.f983 · Cited by 369 · see citing works
Pind, S., Riordan, J. R., & Williams, D. B. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99944-8 · Cited by 360 · see citing works
Protons, osmolytes, and fitness of internal milieu for protein function
Somero, G. N. (1986) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1986.251.2.r197 · Cited by 340 · see citing works
Yang, Y., Janich, S., Cohn, J. A., et al. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.20.9480 · Cited by 338 · see citing works
Solubility as a Function of Protein Structure and Solvent Components
Schein, C. H. (1990) · Nature Biotechnology · doi:10.1038/nbt0490-308 · Cited by 303 · see citing works
Finlay, C. A., Hinds, P. W., Tan, T., et al. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.2.531-539.1988 · Cited by 301 · see citing works
Chemical chaperones interfere with the formation of scrapie prion protein.
Tatzelt, J., Prusiner, S. B., & Welch, W. J. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01027.x · Cited by 294 · see citing works
Self-citationAccumulation of p53 in a Mutant Cell Line Defective in the Ubiquitin Pathway
Chowdary, D., Dermody, J. J., Jha, K. K., & Ozer, H. L. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.3.1997 · Cited by 278 · see citing works
The cystic fibrosis mutation (ΔF508) does not influence the chloride channel activity of CFTR
Li, C., Ramjeesingh, M., Reyes, E., et al. (1993) · Nature Genetics · doi:10.1038/ng0493-311 · Cited by 191 · see citing works
Cannon, J. V., & Lane, D. P. (1991) · Nature · doi:10.1038/349802a0 · Cited by 181 · see citing works
Kulka, R. G., Raboy, B., Schuster, R., Parag, H. A., Diamond, G., Ciechanover, A. J., & Marcus, M. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)37648-3 · Cited by 175 · see citing works
Thermodynamic stability and point mutations of bacteriophage T4 lysozyme
Hawkes, R. B., Grütter, M. G., & Schellman, J. A. (1984) · Journal of Molecular Biology · doi:10.1016/0022-2836(84)90474-1 · Cited by 149 · see citing works
Increased Thermal Stability of Collagen in the Presence of Sugars and Polyols1
Gekko, K., & Koga, S. (1983) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a134330 · Cited by 144 · see citing works
Edington, B. V., Whelan, S. A., & Hightower, L. E. (1989) · Journal of Cellular Physiology · doi:10.1002/jcp.1041390202 · Cited by 139 · see citing works
OSMOTIC-REMEDIAL MUTANTS. A NEW CLASSIFICATION FOR NUTRITIONAL MUTANTS IN YEAST
Hawthorne, D. C., & Friis, J. (1964) · Genetics · doi:10.1093/genetics/50.5.829 · Cited by 100 · see citing works
Accumulation of p53 in a Mutant Cell Line Defective in the Ubiquitin Pathway
Chowdary, D., Dermody, J. J., Jha, K. K., et al. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.3.1997-2003.1994 · Cited by 92 · see citing works
Thermostability of Temperature-sensitive Folding Mutants of the P22 Tailspike Protein
Sturtevant, J. M., Yu, M., Haase‐Pettingell, C., et al. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)81678-7 · Cited by 90 · see citing works
Stephen, A. G., Trausch‐Azar, J. S., Ciechanover, A. J., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.26.15608 · Cited by 55 · see citing works
Ac, M., Qureshi, S. A., Foster, D. A., et al. (1992) · PubMed · Cited by 33 · see citing works
Protection against heat-induced cell killing by polyols in vitro.
Henle, K. J., Peck, J. W., & Higashikubo, R. (1983) · PubMed · Cited by 28 · see citing works
Protection of heat induced cytoxicity by glycerol
Lin, P., Kwock, L., & Hefter, K. (1981) · Journal of Cellular Physiology · doi:10.1002/jcp.1041080318 · Cited by 22 · see citing works
Gerlsma, S. Y., & Stuur, E. R. (1976) · International journal of peptide & protein research · doi:10.1111/j.1399-3011.1976.tb02474.x · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk
Zhu, W., Gregory, J. C., Org, E., Buffa, J. A., Gupta, N., Wang, Z., Li, L., Fu, X., Wu, Y., Mehrabian, M., et al. (2016) · Cell · doi:10.1016/j.cell.2016.02.011 · Cited by 1,968 · see citing works
Targeting mutant p53 for efficient cancer therapy
Bykov, V. J. N., Eriksson, S. E., Bianchi, J., & Wiman, K. G. (2018) · Nature Reviews Cancer · doi:10.1038/nrc.2017.109 · Cited by 889 · see citing works
Progressive disruption of cellular protein folding in models of polyglutamine diseases
Gidalevitz, T., Ben-Zvi, A., Ho, K. H., Brignull, H. R., & Morimoto, R. I. (2006) · Science · doi:10.1126/science.1124514 · Cited by 643 · see citing works
A mouse model to test the in vivo efficacy of chemical chaperones
Bai, C., Biwersi, J., Verkman, A. S., & Matthay, M. A. (1998) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/s1056-8719(98)00034-3 · Cited by 59 · see citing works
Restored mutant receptor:Corticoid binding in chaperone complexes by trimethylamine N-oxide
Miller, A. L., Elam, W. A., Johnson, B. H., Khan, S. H., Kumar, R., & Thompson, E. B. (2017) · PLOS ONE · doi:10.1371/journal.pone.0174183 · Cited by 5 · see citing works
- Authors
- Brown, C. R., Hong-Brown, L. Q., & Welch, W. J.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1997-03-15
- Volume
- 99
- Issue
- 6
- Pages
- 1432-1444
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC507959
- OpenAlex
- W2092291840
- Cited by
- 176
- References
- 37
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 5 · 2017: 6 · 2016: 5 · 2015: 1 · 2014: 3 · 2013: 5 · 2012: 3
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cystic Fibrosis Research
- National Institutes of Health
- National Institute of General Medical Sciences (GM33551, R01GM033551)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Keywords
- ΔF508-CFTR, cystic fibrosis, p53, pp60src, E1 ubiquitin-activating enzyme, glycerol, trimethylamine N-oxide, heavy water, protein misfolding
- MeSH terms
- Animals, Cell Line, Glycerol, Ligases, Methylamines, Mutation, Temperature, Tumor Suppressor Protein p53, Proto-Oncogene Proteins pp60(c-src), Protein Folding, Deuterium Oxide, Ubiquitin-Activating Enzymes, Ubiquitin-Protein Ligases, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
