A Structural Rationale for Selective Stabilization of Anti-tumor Interactions of 14-3-3 proteins by Cotylenin A
Abstract
Cotylenin A, a fungal metabolite originally described as a cytokinin-like bioactive substance against plants shows differentiation-inducing and anti-tumor activity in certain human cancers. Here, we present the crystal structure of cotylenin A acting on a 14-3-3 regulatory protein complex. By comparison with the closely related, but non-anticancer agent fusicoccin A, a rationale for the activity of cotylenin A in human cancers is presented. This class of fusicoccane diterpenoids are possible general modulators of 14-3-3 protein-protein interactions. In this regard, specificities for individual 14-3-3/target protein complexes might be achieved by varying the substituent pattern of the diterpene ring system. As the different activities of fusicoccin A and cotylenin A in human cancers suggest, hydroxylation of C12 might be a sufficient determinant of structural specificity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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 [84]
Cotylenin diterpenes form interfaces between the 14-3-3 protein family and a variety of interacting partners.
“The cotylenin diterpenes form interfaces between the 14-3-3 protein family and a variety of interacting partners 8.”
From Manumycin polyketides act as molecular glues between UBR7 and P53 (2020) · cites this paper as [8]
Cites
<i>Coot</i> : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571 · see citing works
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
Murshudov, G. N., Vagin, A. A., & Dodson, E. J. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444996012255 · Cited by 14,671 · see citing works
Kabsch, W. (1993) · Journal of Applied Crystallography · doi:10.1107/s0021889893005588 · Cited by 3,562 · see citing works
Peng, C.-Y., Graves, P. R., Thoma, R. S., Wu, Z., Shaw, A. S., & Piwnica-Worms, H. (1997) · Science · doi:10.1126/science.277.5331.1501 · Cited by 1,341 · see citing works
Sanchez, Y., Wong, C., Thoma, R. S., Richman, R., Wu, Z., Piwnica-Worms, H., & Elledge, S. J. (1997) · Science · doi:10.1126/science.277.5331.1497 · Cited by 1,320 · 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
Disruption of differentiation in human cancer: AML shows the way
Tenen, D. G. (2003) · Nature Reviews Cancer · doi:10.1038/nrc989 · Cited by 612 · see citing works
Rittinger, K., Budman, J., Xu, J., Volinia, S., Cantley, L. C., Smerdon, S. J., Gamblin, S. J., & Yaffe, M. B. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80363-9 · Cited by 506 · see citing works
Jin, J., Smith, F. D., Stark, C., Wells, C. D., Fawcett, J. P., Kulkarni, S., Metalnikov, P. S., O’Donnell, P. A., Taylor, P., Taylor, L., et al. (2004) · Current Biology · doi:10.1016/j.cub.2004.07.051 · Cited by 448 · see citing works
RUBIO, M. P., Geraghty, K. M., WONG, B. H. C., Wood, N. T., Campbell, D. G., MORRICE, N. A., & MacKintosh, C. (2004) · Biochemical Journal · doi:10.1042/bj20031797 · Cited by 443 · 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
Activation of Raf-1 by 14-3-3 proteins
Fantl, W. J., Muslin, A. J., Kikuchi, A., Martin, J. A., MacNicol, A. M., Grosst, R. W., & Williams, L. T. (1994) · Nature · doi:10.1038/371612a0 · Cited by 367 · 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
Self-citationO'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
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-citationJahn, T. P., Fuglsang, A. T., Olsson, A., Brüntrup, I. M., Collinge, D. B., Volkmann, D., Sommarin, M., Palmgren, M. B., & Larsson, C. U. (1997) · The Plant Cell · doi:10.1105/tpc.9.10.1805 · Cited by 249 · see citing works
14-3-3 proteins associate with cdc25 phosphatases.
Conklin, D. S., Galaktionov, K. I., & Beach, D. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.17.7892 · Cited by 246 · see citing works
Ganguly, S., Weller, J. L., Ho, A., Chemineau, P., Malpaux, B., & Klein, D. C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406871102 · Cited by 220 · see citing works
14-3-3 proteins as potential oncogenes
Tzivion, G., Gupta, V. S., Kaplun, L., & Balan, V. (2006) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2006.03.004 · Cited by 218 · see citing works
Comprehensive Proteomic Analysis of Interphase and Mitotic 14-3-3-binding Proteins
Meek, S. E. M., Lane, W. S., & Piwnica-Worms, H. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403044200 · Cited by 211 · see citing works
Targeted Proteomic Analysis of 14-3-3ς, a p53 Effector Commonly Silenced in Cancer
Benzinger, A., Muster, N., Koch, H., Yates, J. R., & Hermeking, H. (2005) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500021-mcp200 · Cited by 181 · see citing works
Fusicoccin: a New Wilting Toxin produced by Fusicoccum amygdali Del.
BALLIO, A., Chain, E. B., Leo, P. D., ERLANGER, B. F., MAURI, M., & TONOLO, A. (1964) · Nature · doi:10.1038/203297a0 · Cited by 177 · 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-citationTopology and target interaction of the fusicoccin‐binding 14‐3‐3 homologs of Commelina communis
Oecking, C., Piotrowski, M., Hagemeier, J., et al. (1997) · The Plant Journal · doi:10.1046/j.1365-313x.1997.12020441.x · Cited by 133 · see citing works
Self-citationAkt and 14-3-3η regulate Miz1 to control cell-cycle arrest after DNA damage
Wanzel, M., Kleine‐Kohlbrecher, D., Herold, S., Hock, A., Berns, K., Park, J., Hemmings, B. A., & Eilers, M. (2004) · Nature Cell Biology · doi:10.1038/ncb1202 · Cited by 77 · see citing works
Isolation of a New Plant Growth Substance with Cytokinin-like Activity
Sassa, T., TOJYO, T., & Munakata, K. (1970) · Nature · doi:10.1038/227379a0 · Cited by 71 · see citing works
Self-citationAsahi, K., Honma, Y., Hazeki, K., Sassa, T., Kubohara, Y., Sakurai, A., & Takahashi, N. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7385 · Cited by 71 · see citing works
Self-citationKasukabe, T., Okabe‐Kado, J., Kato, N., Sassa, T., & Honma, Y. (2005) · Breast Cancer Research · doi:10.1186/bcr1344 · Cited by 62 · see citing works
Self-citationHonma, Y., Ishii, Y., Yamamoto-Yamaguchi, Y., Sassa, T., & Asahi, K. (2003) · PubMed · Cited by 51 · see citing works
Self-citationYamada, K., Honma, Y., Asahi, K., Sassa, T., Hino, K., & Tomoyasu, S. (2001) · British Journal of Haematology · doi:10.1046/j.1365-2141.2001.03029.x · Cited by 49 · see citing works
Self-citationHonma, Y., Kasukabe, T., Yamori, T., et al. (2005) · Gynecologic Oncology · doi:10.1016/j.ygyno.2005.07.015 · Cited by 33 · see citing works
Honma, Y., Ishii, Y., Sassa, T., & Asahi, K. (2003) · Leukemia Research · doi:10.1016/s0145-2126(03)00071-7 · Cited by 33 · see citing works
Self-citationTajima, N., Nukina, M., Kato, N., et al. (2004) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.68.1125 · Cited by 14 · see citing works
Self-citation
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
Manumycin polyketides act as molecular glues between UBR7 and P53
Isobe, Y., Okumura, M., McGregor, L. M., Brittain, S. M., Jones, M. D., Liang, X., White, R., Forrester, W., McKenna, J. M., Tallarico, J. A., et al. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0557-2 · Cited by 124 · see citing works
Anders, C., Higuchi, Y., Koschinsky, K., Bartel, M., Schumacher, B., Thiel, P., Nitta, H., Preisig-Müller, R., Schlichthörl, G., Renigunta, V., et al. (2013) · Chemistry & Biology · doi:10.1016/j.chembiol.2013.03.015 · Cited by 106 · see citing works
Self-citationStabilization and Inhibition of Protein–Protein Interactions: The 14-3-3 Case Study
Milroy, L.-G., Brunsveld, L., & Ottmann, C. (2013) · ACS Chemical Biology · doi:10.1021/cb300599t · Cited by 88 · see citing works
Self-citationSmall 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
- Ottmann, C., Weyand, M., Sassa, T., Inoue, T., Kato, N., Wittinghofer, A., & Oecking, C.
- Affiliations
- Max Planck Society (DE)
- Yamagata University (JP)
- The Institute of Scientific and Industrial Research, The University of Osaka (JP)
- Max Planck Institute of Molecular Physiology (DE)
- University of Tübingen (DE)
- Corresponding author
- Ottmann, Christian
- Oecking, Claudia
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 386
- Issue
- 4
- Pages
- 913-919
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W2039369286
- Cited by
- 94
- References
- 35
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 6 · 2021: 8 · 2020: 6 · 2019: 6 · 2018: 5 · 2017: 6 · 2016: 1 · 2015: 8 · 2014: 7 · 2013: 3 · 2012: 7
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- TU/e Research Portal (publishedVersion)
- TU/e Research Portal (submittedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 14-3-3 protein interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Physical Sciences › Chemistry › Inorganic Chemistry › Crystal structures of chemical compounds
- Keywords
- 14-3-3 proteins, fusicoccin A, protein-protein interaction, anticancer activity, crystal structure, structure-activity relationship, fungal metabolites
- MeSH terms
- Amino Acid Sequence, Antineoplastic Agents, Calorimetry, Diterpenes, Glycosides, Proton-Translocating ATPases, Humans, Models, Molecular, Molecular Sequence Data, Phosphopeptides, Protein Binding, Structure-Activity Relationship, Nicotiana, Protein Structure, Secondary, Crystallography, X-Ray, Amino Acid Motifs, 14-3-3 Proteins, Protein Multimerization, 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