A Semisynthetic Fusicoccane Stabilizes a Protein-Protein Interaction and Enhances the Expression of K+ Channels at the Cell Surface
Open accessAbstract
Small-molecule stabilization of protein-protein interactions is an emerging field in chemical biology. We show how fusicoccanes, originally identified as fungal toxins acting on plants, promote the interaction of 14-3-3 proteins with the human potassium channel TASK-3 and present a semisynthetic fusicoccane derivative (FC-THF) that targets the 14-3-3 recognition motif (mode 3) in TASK-3. In the presence of FC-THF, the binding of 14-3-3 proteins to TASK-3 was increased 19-fold and protein crystallography provided the atomic details of the effects of FC-THF on this interaction. We also tested the functional effects of FC-THF on TASK channels heterologously expressed in Xenopus oocytes. Incubation with 10 μM FC-THF was found to promote the transport of TASK channels to the cell membrane, leading to a significantly higher density of channels at the surface membrane and increased potassium current.
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?
Fusicoccanes induce targeted stabilization between 14-3-3 proteins and part of their interactome.
“Often called ''chemical stabilizers'', fusicoccanes (e.g., fusicoccin A, cotylenin A) induce the targeted stabilization between the 14-3-3 proteins and part of its interactome (Fig. 4).[83][84][85]”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [85]
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
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 · see citing works
An inhibitor of Bcl-2 family proteins induces regression of solid tumours
Oltersdorf, T., Elmore, S. W., Shoemaker, A. R., Armstrong, R. C., Augeri, D. J., Belli, B., Bruncko, M., Deckwerth, T. L., Dinges, J., Hajduk, P. J., et al. (2005) · Nature · doi:10.1038/nature03579 · Cited by 3,407 · see citing works
Reaching for high-hanging fruit in drug discovery at protein–protein interfaces
Wells, J. A., & McClendon, C. L. (2007) · Nature · doi:10.1038/nature06526 · Cited by 1,963 · see citing works
The Structural Basis for 14-3-3:Phosphopeptide Binding Specificity
Yaffe, M. B., Rittinger, K., Volinia, S., Caron, P. R., Aitken, A., Leffers, H. C. B., Gamblin, S. J., Smerdon, S. J., & Cantley, L. C. (1997) · Cell · doi:10.1016/s0092-8674(00)80487-0 · Cited by 1,604 · see citing works
Structure of the FKBP12-Rapamycin Complex Interacting with Binding Domain of Human FRAP
Choi, J., Chen, J., Schreiber, S. L., & Clardy, J. (1996) · Science · doi:10.1126/science.273.5272.239 · Cited by 933 · see citing works
X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex
Griffith, J. P., Kim, J. L., Kim, E. E., Sintchak, M. D., Thomson, J. A., Fitzgibbon, M. J., Fleming, M. A., Caron, P. R., Hsiao, K., & Navia, M. A. (1995) · Cell · doi:10.1016/0092-8674(95)90439-5 · Cited by 834 · see citing works
Vassilev, A., Kaneko, K. J., Shu, H., Zhao, Y., & DePamphilis, M. L. (2001) · Genes & Development · doi:10.1101/gad.888601 · Cited by 719 · see citing works
TASK, a human background K+ channel to sense external pH variations near physiological pH
Duprat, F., Lesage, F., Fink, M., Reyes, R. V., Heurteaux, C., & Lazdunski, M. (1997) · The EMBO Journal · doi:10.1093/emboj/16.17.5464 · Cited by 629 · see citing works
14-3-3 proteins in the nervous system
Berg, D., Holzmann, C., & Rieß, O. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1197 · Cited by 619 · see citing works
Hermeking, H. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1230 · Cited by 434 · see citing works
Binding of 14-3-3 Proteins to the Protein Kinase Raf and Effects on Its Activation
Freed, E., Symons, M. H., Macdonald, S. G., McCormick, F. P., & Ruggieri, R. (1994) · Science · doi:10.1126/science.8085158 · Cited by 414 · see citing works
Structural view of a fungal toxin acting on a 14‐3‐3 regulatory complex
Würtele, M., Jelich-Ottmann, C., Wittinghofer, A., & Oecking, C. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg104 · Cited by 349 · see citing works
Bioinformatic and experimental survey of 14-3-3-binding sites
Johnson, C., Crowther, S., Stafford, M. J., Campbell, D. G., Toth, R. L., & MacKintosh, C. (2010) · Biochemical Journal · doi:10.1042/bj20091834 · Cited by 337 · see citing works
TASK-3, a Novel Tandem Pore Domain Acid-sensitive K+Channel
Rajan, S., Wischmeyer, E., Liu, G. X., Preisig‐Müller, R., Daut, J., Karschin, A., & Derst, C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000030200 · Cited by 317 · see citing works
Self-citation14-3-3 proteins in cell cycle regulation
Hermeking, H., & Benzinger, A. (2006) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2006.03.002 · Cited by 307 · see citing works
O'Kelly, I., Butler, M. H., Zilberberg, N., & Goldstein, S. A. N. (2002) · Cell · doi:10.1016/s0092-8674(02)01040-1 · Cited by 275 · see citing works
Fu, H., Coburn, J., & Collier, R. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.6.2320 · Cited by 267 · see citing works
Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene
Mu, D., Chen, L., Zhang, X., See, L.-H., Koch, C. M., Yen, C., Tong, J. J., Spiegel, L. A., Nguyen, K. C. Q., Servoss, A., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00054-0 · Cited by 263 · see citing works
Ottmann, C., Marco, S., Jaspert, N., Marcon, C., Schauer, N., Weyand, M., Vandermeeren, C., Duby, G., Boutry, M., Wittinghofer, A., et al. (2007) · Molecular Cell · doi:10.1016/j.molcel.2006.12.017 · Cited by 255 · see citing works
Self-citationThiel, P., Kaiser, M., & Ottmann, C. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201107616 · Cited by 207 · see citing works
Self-citationK+-dependent Cerebellar Granule Neuron Apoptosis
Lauritzen, I., Zanzouri, M., Honoré, É., Duprat, F., Ehrengruber, M. U., Lazdunski, M., & Patel, A. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302631200 · Cited by 193 · see citing works
Barel, O., Shalev, S. A., Ofir, R., Cohen, A., Zlotogora, J., Shorer, Z., Mazor, G., Finer, G., Khateeb, S., Zilberberg, N., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.07.010 · Cited by 190 · see citing works
Neuronal two‐pore‐domain potassium channels and their regulation by G protein‐coupled receptors
Mathie, A. A. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.121582 · Cited by 189 · see citing works
Oncogenic potential of TASK3 ( Kcnk9 ) depends on K + channel function
Pei, L., Wiser, O., Slavin, A., Mu, D., Powers, S., Jan, L. Y., & Hoey, T. C. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1232448100 · Cited by 172 · see citing works
Meuth, S. G., Budde, T., Kanyshkova, T. G., Broicher, T., Munsch, T., & Pape, H. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-16-06460.2003 · Cited by 170 · see citing works
Ottmann, C., Yasmin, L., Weyand, M., Veesenmeyer, J. L., Diaz, M. H., Palmer, R. H., Francis, M. S., Hauser, A. R., Wittinghofer, A., & Hallberg, B. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601530 · Cited by 164 · see citing works
Self-citationRajan, S., Preisig‐Müller, R., Wischmeyer, E., Nehring, R. B., Hanley, P. J., Renigunta, V., Musset, B., Schlichthörl, G., Derst, C., Karschin, A., et al. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.027052 · Cited by 154 · see citing works
Self-citationThe 2P-domain K + channels: role in apoptosis and tumorigenesis
Patel, A. J., & Lazdunski, M. (2004) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-004-1255-8 · Cited by 153 · see citing works
Chibby cooperates with 14-3-3 to regulate β-catenin subcellular distribution and signaling activity
Li, F., Mofunanya, A., Harris, K., & Takemaru, K. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200709091 · Cited by 140 · see citing works
Molzan, M., Schumacher, B., Ottmann, C., Baljuls, A., Polzien, L., Weyand, M., Thiel, P., Rose, R., Rose, M., Kuhenne, P., et al. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.01636-09 · Cited by 127 · see citing works
Self-citationFusicoccanes: diterpenes with surprising biological functions
BOER, A. H. D., & Leeuwen, I. J. D. V.-V. (2012) · Trends in Plant Science · doi:10.1016/j.tplants.2012.02.007 · Cited by 107 · see citing works
Renigunta, V., Yuan, H., Zuzarte, M., et al. (2005) · Traffic · doi:10.1111/j.1600-0854.2005.00375.x · Cited by 98 · see citing works
Self-citationOttmann, C., Weyand, M., Sassa, T., Inoue, T., Kato, N., Wittinghofer, A., & Oecking, C. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.01.005 · Cited by 94 · see citing works
Self-citationMolecular Physiology of pH-Sensitive Background K2PChannels
Lesage, F., & Barhanin, J. (2011) · Physiology · doi:10.1152/physiol.00029.2011 · Cited by 94 · see citing works
Structure of the p53 C‐terminus bound to 14‐3‐3: Implications for stabilization of the p53 tetramer
Schumacher, B., Mondry, J., Thiel, P., Weyand, M., & Ottmann, C. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.02.065 · Cited by 89 · see citing works
Self-citationZuzarte, M., Heusser, K., Renigunta, V., et al. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2008.164756 · Cited by 82 · see citing works
Self-citationTASK-3 Channel Deletion in Mice Recapitulates Low-Renin Essential Hypertension
Guagliardo, N. A., Yao, J., Hu, C., Schertz, E. M., Tyson, D. A., Carey, R. M., Bayliss, D. A., & Barrett, P. Q. (2012) · Hypertension · doi:10.1161/hypertensionaha.111.189662 · Cited by 79 · see citing works
Membrane Proteins as 14-3-3 Clients in Functional Regulation and Intracellular Transport
Smith, A. J., Daut, J., & Schwappach, B. (2011) · Physiology · doi:10.1152/physiol.00042.2010 · Cited by 75 · see citing works
Self-citationMechanistic differences in the transcriptional activation of p53 by 14-3-3 isoforms
Rajagopalan, S., Sade, R. S., Townsley, F. M., & Fersht, A. R. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp1041 · Cited by 71 · see citing works
From the Background to the Spotlight: TASK Channels in Pathological Conditions
Bittner, S., Budde, T., Wiendl, H., & Meuth, S. G. (2010) · Brain Pathology · doi:10.1111/j.1750-3639.2010.00407.x · Cited by 71 · see citing works
Genetic isolation of transport signals directing cell surface expression
Shikano, S., Coblitz, B., Sun, H., & Li, M. (2005) · Nature Cell Biology · doi:10.1038/ncb1297 · Cited by 68 · see citing works
Ruf, N., Bähring, S., Galetzka, D., Pliushch, G., Luft, F. C., Nürnberg, P., Haaf, T., Kelsey, G., & Zechner, U. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm216 · Cited by 66 · see citing works
Structure of a 14-3-3σ–YAP phosphopeptide complex at 1.15 Å resolution
Schumacher, B., Skwarczynska, M., Rose, R., & Ottmann, C. (2010) · Acta Crystallographica Section F Structural Biology and Crystallization Communications · doi:10.1107/s1744309110025479 · Cited by 55 · see citing works
Self-citationTASK-3 as a potential antidepressant target
Gotter, A. L., Santarelli, V. P., Doran, S. M., Tannenbaum, P. L., Kraus, R. L., Rosahl, T. W., Méziane, H., Montial, M., Reiss, D. R., Wessner, K., et al. (2011) · Brain Research · doi:10.1016/j.brainres.2011.08.021 · Cited by 46 · see citing works
Deafness associated changes in two-pore domain potassium channels in the rat inferior colliculus
Cui, Y. L., Holt, A. G., Lomax, C. A., & Altschuler, R. A. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.05.054 · Cited by 42 · see citing works
Forward Transport of K2P3.1: Mediation by 14‐3‐3 and COPI, Modulation by p11
Kelly, A. M., & Goldstein, S. A. N. (2007) · Traffic · doi:10.1111/j.1600-0854.2007.00663.x · Cited by 38 · see citing works
Zanzouri, M., Lauritzen, I., Duprat, F., Mazzuca, M., Lesage, F., Lazdunski, M., & Patel, A. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606092200 · Cited by 34 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Modulators of Protein–Protein Interactions
Milroy, L.-G., Grossmann, T. N., Hennig, S., Brunsveld, L., & Ottmann, C. (2014) · Chemical Reviews · doi:10.1021/cr400698c · Cited by 497 · see citing works
Self-citationChasing molecular glue degraders: screening approaches
Domostegui, A., Nieto-Barrado, L., Perez-Lopez, C., & Mayor-Ruiz, C. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00197g · Cited by 200 · see citing works
Small molecule modulators of protein-protein interactions: selected case studies
Aeluri, M., Chamakuri, S., Dasari, B., Guduru, S. K. R., Jimmidi, R., Jogula, S., & Arya, P. (2014) · Chemical Reviews · doi:10.1021/cr4004049 · Cited by 79 · see citing works
Small molecules targeting protein–protein interactions for cancer therapy
Wu, D., Li, Y., Zheng, L., Xiao, H., Ouyang, L., Wang, G., & Sun, Q. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.05.035 · Cited by 71 · see citing works
- Authors
- Anders, C., Higuchi, Y., Koschinsky, K., Bartel, M., Schumacher, B., Thiel, P., Nitta, H., Preisig-Müller, R., Schlichthörl, G., Renigunta, V., Ohkanda, J., Daut, J., Kato, N., & Ottmann, C.
- Affiliations
- Max Planck Society (DE)
- The Institute of Scientific and Industrial Research, The University of Osaka (JP)
- Philipps University of Marburg (DE)
- Corresponding author
- Daut, Jürgen
- Kato, Nobuo
- Ottmann, Christian
- ORCID
- Venue
- Chemistry & Biology
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 20
- Issue
- 4
- Pages
- 583-593
- ISSN
- 1074-5521 (ISSN-L)
- OpenAlex
- W2159219455
- Cited by
- 106
- References
- 47
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 8 · 2023: 14 · 2022: 6 · 2021: 7 · 2020: 9 · 2019: 6 · 2018: 11 · 2017: 12 · 2016: 3 · 2015: 11 · 2014: 9 · 2013: 1
- FWCI
- 3.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Chemistry & Biology (publishedVersion)
- PubMed (publishedVersion)
- TU/e Research Portal (publishedVersion, other-oa)
- TU/e Research Portal (submittedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- TU/e Research Portal (submittedVersion, other-oa)
- Funders
- AstraZeneca
- Merck KGaA
- Bayer HealthCare
- Deutsche Forschungsgemeinschaft (SFB593, FOR 1086)
- National Institute of Biomedical Innovation
- Bayer CropScience
- Japan Society for the Promotion of Science (22350074, 24102519)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 14-3-3 protein interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- 14-3-3 proteins, mycotoxins, potassium currents, small molecule binding
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Biological Transport, Cell Membrane, Diterpenes, Humans, Kinetics, Molecular Conformation, Molecular Sequence Data, Oocytes, Protein Binding, Xenopus laevis, Protein Structure, Tertiary, Crystallography, X-Ray, Potassium Channels, Tandem Pore Domain, 14-3-3 Proteins, Protein Interaction Domains and Motifs, Protein Stability
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