Effective and sustained inhibition of non-enzymatic oncogenic driver proteins is a major pharmacological challenge. The clinical success of thalidomide analogues demonstrates the therapeutic efficacy of drug-induced degradation of transcription factors and other cancer targets1,2,3, but a substantial subset of proteins are resistant to targeted degradation using existing approaches4,5. Here we report an alternative mechanism of targeted protein degradation, in which a small molecule induces the highly specific, reversible polymerization of a target protein, followed by its sequestration into cellular foci and subsequent degradation. BI-3802 is a small molecule that binds to the Broad-complex, Tramtrack and Bric-à-brac (BTB) domain of the oncogenic transcription factor B cell lymphoma 6 (BCL6) and leads to the proteasomal degradation of BCL66. We use cryo-electron microscopy to reveal how the solvent-exposed moiety of a BCL6-binding molecule contributes to a composite ligand–protein surface that engages BCL6 homodimers to form a supramolecular structure. Drug-induced formation of BCL6 filaments facilitates ubiquitination by the SIAH1 E3 ubiquitin ligase. Our findings demonstrate that a small molecule such as BI-3802 can induce polymerization coupled to highly specific protein degradation, which in the case of BCL6 leads to increased pharmacological activity compared to the effects induced by other BCL6 inhibitors. These findings open new avenues for the development of therapeutic agents and synthetic biology.
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Structural data have been deposited to the Electron Microscopy Data Bank (EMDB; EMD-22265) and the RCSB PDB (6XMX). Proteome quantification data are available in the PRIDE repository (https://www.ebi.ac.uk/pride/archive; PXD016185). Uncropped gel and western blot data are shown in Supplementary Fig. 1, and the flow cytometry gating strategy is shown in Supplementary Fig. 2.
The scripts used for modelling and analysis in this study are available on Github (https://github.com/fischerlab/scripts-publications/tree/master/2020_BCL6_polymerization).
Krönke, J. et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science 343, 301–305 (2014).
Lu, G. et al. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science 343, 305–309 (2014).
Krönke, J. et al. Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS. Nature 523, 183–188 (2015).
Huang, H.-T. et al. A chemoproteomic approach to query the degradable kinome using a multi-kinase degrader. Cell Chem. Biol. 25, 88–99 (2018).
McCoull, W. et al. Development of a novel B-cell lymphoma 6 (BCL6) PROTAC to provide insight into small molecule targeting of BCL6. ACS Chem. Biol. 13, 3131–3141 (2018).
Kerres, N. et al. Chemically induced degradation of the oncogenic transcription factor BCL6. Cell Rep. 20, 2860–2875 (2017).
Toure, M. & Crews, C. M. Small-molecule PROTACS: new approaches to protein degradation. Angew. Chem. Int. Edn Engl. 55, 1966–1973 (2016).
Bondeson, D. P. et al. Catalytic in vivo protein knockdown by small-molecule PROTACs. Nat. Chem. Biol. 11, 611–617 (2015).
Winter, G. E. et al. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science 348, 1376–1381 (2015).
Nowak, R. P. et al. Plasticity in binding confers selectivity in ligand-induced protein degradation. Nat. Chem. Biol. 14, 706–714 (2018).
Petzold, G., Fischer, E. S. & Thomä, N. H. Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase. Nature 532, 127–130 (2016).
Sievers, Q. L. et al. Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN. Science 362, eaat0572 (2018).
Cerchietti, L. C. et al. A small-molecule inhibitor of BCL6 kills DLBCL cells in vitro and in vivo. Cancer Cell 17, 400–411 (2010).
Cardenas, M. G. et al. Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma. J. Clin. Invest. 126, 3351–3362 (2016).
Bosga-Bouwer, A. G. et al. BCL6 alternative translocation breakpoint cluster region associated with follicular lymphoma grade 3B. Genes Chromosom. Cancer 44, 301–304 (2005).
Hatzi, K. & Melnick, A. Breaking bad in the germinal center: how deregulation of BCL6 contributes to lymphomagenesis. Trends Mol. Med. 20, 343–352 (2014).
Cattoretti, G. et al. Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice. Cancer Cell 7, 445–455 (2005).
Ranuncolo, S. M., Polo, J. M. & Melnick, A. BCL6 represses CHEK1 and suppresses DNA damage pathways in normal and malignant B-cells. Blood Cells Mol. Dis. 41, 95–99 (2008).
Tunyaplin, C. et al. Direct repression of prdm1 by Bcl-6 inhibits plasmacytic differentiation. J. Immunol. 173, 1158–1165 (2004).
Phan, R. T., Saito, M., Basso, K., Niu, H. & Dalla-Favera, R. BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells. Nat. Immunol. 6, 1054–1060 (2005).
Schlager, S. et al. Inducible knock-out of BCL6 in lymphoma cells results in tumor stasis. Oncotarget 11, 875–890 (2020).
Ghetu, A. F. et al. Structure of a BCOR corepressor peptide in complex with the BCL6 BTB domain dimer. Mol. Cell 29, 384–391 (2008).
Sievers, Q. L., Gasser, J. A., Cowley, G. S., Fischer, E. S. & Ebert, B. L. Genome-wide screen identifies cullin-RING ligase machinery required for lenalidomide-dependent CRL4CRBN activity. Blood 132, 1293–1303 (2018).
Hunkeler, M. et al. Structural basis for regulation of human acetyl-CoA carboxylase. Nature 558, 470–474 (2018).
House, C. M. et al. A binding motif for Siah ubiquitin ligase. Proc. Natl Acad. Sci. USA 100, 3101–3106 (2003).
Ji, L. et al. The SIAH E3 ubiquitin ligases promote Wnt/β-catenin signaling through mediating Wnt-induced Axin degradation. Genes Dev. 31, 904–915 (2017).
Garcia-Seisdedos, H., Empereur-Mot, C., Elad, N. & Levy, E. D. Proteins evolve on the edge of supramolecular self-assembly. Nature 548, 244–247 (2017).
Słabicki, M. et al. The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K. Nature 585, 293–297 (2020).
Bellenie, B. R. et al. Achieving in vivo target depletion through the discovery and optimization of benzimidazolone BCL6 degraders. J. Med. Chem. 63, 4047–4068 (2020).
Meyers, R. M. et al. Computational correction of copy number effect improves specificity of CRISPR–Cas9 essentiality screens in cancer cells. Nat. Genet. 49, 1779–1784 (2017).
Donovan, K. A. et al. Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. eLife 7, e38430 (2018).
Abdulrahman, W. et al. A set of baculovirus transfer vectors for screening of affinity tags and parallel expression strategies. Anal. Biochem. 385, 383–385 (2009).
Faust, T. B. et al. Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15. Nat. Chem. Biol. 16, 7–14 (2020).
Marze, N. A., Roy Burman, S. S., Sheffler, W. & Gray, J. J. Efficient flexible backbone protein-protein docking for challenging targets. Bioinformatics 34, 3461–3469 (2018).
Enkhbayar, P., Damdinsuren, S., Osaki, M. & Matsushima, N. HELFIT: helix fitting by a total least squares method. Comput. Biol. Chem. 32, 307–310 (2008).
Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).
Rohou, A. & Grigorieff, N. CTFFIND4: fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216–221 (2015).
Wagner, T. et al. SPHIRE-crYOLO is a fast and accurate fully automated particle picker for cryo-EM. Commun. Biol. 2, 218 (2019).
Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).
Tan, Y. Z. et al. Addressing preferred specimen orientation in single-particle cryo-EM through tilting. Nat. Methods 14, 793–796 (2017).
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010).
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213–221 (2010).
Doench, J. G. et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR–Cas9. Nat. Biotechnol. 34, 184–191 (2016).
Sanjana, N. E., Shalem, O. & Zhang, F. Improved vectors and genome-wide libraries for CRISPR screening. Nat. Methods 11, 783–784 (2014).
Sperling, A. S. et al. Patterns of substrate affinity, competition, and degradation kinetics underlie biological activity of thalidomide analogs. Blood 134, 160–170 (2019).
We thank the Broad Institute Flow Facility (particularly P. Rogers), the Broad Institute Walk-Up Sequencing Team (particularly T. Mason) and the Broad Institute Genetic Perturbation Platform and Whitehead Institute Microscopy Facility (particularly W. Salmon) for technical assistance. Cryo-EM data were collected at the Harvard Cryo-Electron Microscopy Center for Structural Biology. We acknowledge the Research Computing Group at Harvard Medical School for computational modeling, and the SBGrid suite for structural biology software packages. We thank S. Sterling and R. Walsh for microscopy support; S. Rawson for comments and computing support; H.-S. Seo for help with the isothermal calorimetry experiment; and J. Kennedy for providing the sgRNA.SFFV.tBFP backbone. We are grateful to all members of the Ebert and Fischer laboratories for discussion, particularly B. Liddicoat, R. Belizaire, S. Koochaki, Q. L. Sievers, R. S. Sellar, M. Jan, P. M.C. Park, D. Levin and T. B. Faust, as well as N. H. Thomä, G. Petzold, Z. Kozicka, K. Mulvaney, D. Pal, and J. Schmid-Burgk. M.S. has received funding from the European Union’s Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie grant agreement no. 702642; H.Y. was supported by a Chleck Foundation fellowship and is a recipient of the NCI Predoctoral to Postdoctoral Fellow Transition (F99/K00) Award (F99CA253754); S.S.R.B. is the recipient of a Cancer Research Institute Irvington Postdoctoral Fellowship (CRI 3442); A.S.S. is supported by a DF/HCC K12 grant, a Conquer Cancer Foundation Young Investigator Award and an award from the Wong Family Foundation; and M.H. is supported by a Swiss National Science Foundation Fellowship 174331. This work was supported by the National Institutes of Health (NIH) grants R01HL082945, P01CA108631 and P50CA206963 (to B.L.E.), the Howard Hughes Medical Institute, the Edward P. Evans Foundation and the Leukemia and Lymphoma Society (to B.L.E.), NIH grant NCI R01CA214608 (to E.S.F.) and a Mark Foundation Emerging Leader Award 19-001-ELA (grant to E.S.F.).
B.L.E. has received research funding from Celgene and Deerfield. He has received consulting fees from GRAIL, and he serves on the scientific advisory boards for and holds equity in Skyhawk Therapeutics and Exo Therapeutics. He is a founder, member of the scientific advisory board and equity holder of Neomorph. E.S.F. is a founder, member of the scientific advisory board and equity holder of Civetta Therapeutics, Jengu Therapeutics (board member) and Neomorph, holds equity in C4 Therapeutics and is a consultant to Astellas and EcoR1 capital. The Fischer laboratory receives or has received research funding from Novartis, Deerfield, Ajax and Astellas. S.F. has had a consulting or advisory role, received honoraria, research funding and/or funding for travel or accommodation expenses from the following for-profit companies: Bayer, Roche, Amgen, Eli Lilly, PharmaMar, AstraZeneca and Pfizer. M.S., H.Y., J.K., E.S.F. and B.L.E are named as inventors on pending US Provisional Application Nos. 62/938,736 and 63/074,279, filed by The Broad Institute, Inc and Dana Farber Cancer Institute related to this work. The remaining authors declare no competing interests.
Peer review information Nature thanks Ivan Dikic, Frank Sicheri and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Extended data figures and tables
a, Immunoblots of BCL6 levels in cytoplasmic, nuclear or chromatin-bound fractions of SuDHL4Cas9 cells after treatment with DMSO or 1 μM BI-3802 for 24 h (n = 2). b, mRNA levels quantified by qPCR in SuDHL4Cas9 cells after treatment with 1 μM BI-3802 or DMSO for 1 h (bars represent mean and s.d., n = 3). c, Whole-proteome quantification of SuDHL4Cas9 cells treated with 1 μM BI-3812 (n = 1) or DMSO (n = 3) for 4 h (two-sided moderated t-test, n = 3). d, Immunoblots of BCL6 levels in SuDHL4Cas9 cells treated with 10 μM MG132 (26S proteasome inhibitor) for 1 h, 1 μM BI-3802 for 45 min or 10 μM BI-3812 for 10 min. A subset of the polymerized BCL6 was insoluble and lost during the western blot sample preparation, however, treatment with an excess of BI-3812 shortly before protein collection reverted polymerization, solubilized BCL6 and allowed for reliable quantification (n = 2). e, Immunoblots of BCL6 levels in SuDHL4Cas9 cells treated with DMSO, 10 μM MLN7243 (ubiquitin activating enzyme inhibitor), 10 μM MG132 (26S proteasome inhibitor), 10 μM chloroquine (lysosomal inhibitor) or 5 μM MLN4924 (neddylation inhibitor) for 15 min; then, for indicated samples, 1 μM BI-3802 was added and 35 min later, 10 μM BI-3812 was added for the final 10 min, resulting in a total of 1 h treatment with MLN7243, MG132, chloroquine or MLN4924, 45 min with BI-3802 and 10 min with BI-3812 (n = 2). f, Cytospin immunofluorescence images of SuDHL4Cas9 cells treated with DMSO (left) or 0.5 μM MLN7243 for 2 h and 1 μM BI-3802 (right) for 1 h. Scale bar, 5 μm (n = 2). g, Flow cytometry analysis of HEK293TCas9 cells expressing eGFP–BCL6(1–275) that were exposed simultaneously to the indicated concentrations of BI-3802 and BI-3812 for 24 h. Lines represent standard four-parameter log-logistic curve fit (n = 3).
Extended Data Fig. 2 Computational docking of BCL6 helical filament models with distinct binding modes.
Visualization of top-scoring BCL6 BTB domain filament model from three different binding modes: end-to-end (E2E), face-to-end (F2E) and face-to-face (F2F). Each BTB monomer used for building the tetramer model is labelled in a distinct colour. BI-3802 is visualized as a sphere. The interface score is an estimate of the binding energy between the dimers. The helical pitch was calculated by extending the tetramer. Sub-angstrom variations in the F2F binding mode have a profound effect on helical pitch (more than 10 nm).
a, Representative cryo-EM micrograph at −2 μm defocus. Micrograph was low-pass-filtered. Scale bar, 100 nm. b, Local-resolution map of the final reconstruction with a threshold of 0.0154 (Chimera) calculated using RELION v.3.0. c, Data-processing scheme for the BCL6 filaments. Iterative 2D classifications resulted in 274,999 particles. Multiple subsequent rounds of 3D classification, refinement, and polishing improved map resolution to a final overall resolution of 3.7 Å. Percentages refer to the particles in each class. Red density maps indicate the classes that were used for the next round of processing, and blue density maps are from 3D refinements. d, FSC plots for unmasked and masked maps. Overall resolution is indicated at FSC = 0.143. e, Histogram and directional FSC plot for BCL6 cryo-EM map. f, g, Regions of the cryo-EM model for the BCL6 filament fit into the density map, demonstrating side-chain density for multiple residues. Each density is shown at a threshold of 0.0178 (from Chimera).
a, Density for BI-3802 in the 3.7-Å cryo-EM reconstruction. The crystal structure of BCL6 bound to BI-3802 (PDB 5MW2) was docked into the cryo-EM map and refined using phenix.real_space_refine. The cryo-EM density is shown in grey at a threshold of 0.0178 (from Chimera). b, Density of BI-3802 and key interacting residues (Arg28, Glu41, Tyr58, Cys84) for BCL6 polymerization. Each density in mesh is shown at a threshold of 0.0178 (from Chimera). c, d, Comparison of the cryo-EM model of polymerized BCL6 (white) with the BCL6 crystallographic lattice (yellow, PDB 5MW2) for dimer–dimer (c), and filament (d). e, Superimposed structures of BI-3802 (yellow) and BI-3812 (orange) bound to the BCL6 filament. BI-3812 was docked to the crystal structure of BCL6 BTB (PDB 5MW2), which was then aligned to the BI-3802-mediated BCL6 filament model. The solvent-exposed moiety of the inhibitor is clashing with the adjacent BCL6 dimer (grey). f, Preassembled 0.1 μM FITC-labelled BCoR peptide and 0.1 μM biotinylated BCL6(5–129) variants were treated with an increasing concentration of BI-3802, and the signal was measured by TR-FRET. The interaction of BCL6 with the BCOR co-repressor peptide was used to quantitively determine drug binding. Lines represent standard four-parameter log-logistic curve fit (n = 3).
a, Schematic of alanine mutagenesis resistance screen of the BCL6 BTB domain in SuDHL4Cas9 cells. b, Schematic of alanine mutagenesis reporter screen of the BCL6 BTB domain in HEK293TCas9 cells. c, Alanine mutagenesis screen of the BCL6 BTB domain for impaired BI-3802 induced degradation at 1 μM BI-3802 in HEK293TCas9 cells. Mutations that confer resistance are labelled. Four different codons were collapsed to each unique amino acid position (greater than threefold enrichment, P < 10−4; n = 2; four codons per position; two-sided empirical rank-sum test-statistics). d, Correlation of BCL6 mRNA expression (transcripts per million (TPM)) and BCL6 dependency (CERES score) in a set of 559 cancer cell lines from the Dependency Map Project. Cell lines chosen for experiments are labelled. e, SuDHL4Cas9, RajiCas9 (both BCL6-dependent) and DELCas9 (BCL6-independent) cells were infected with the indicated BCL6 variants and treated with 1 μM BI-3802 or DMSO over 21 days. Lines represent measurement from each replicate (n = 2). f, BI-3802 in the polymerization interface. Residues identified in the alanine scan are highlighted, with the following colour code: orange, Gly55, Tyr58 (residues involved in drug binding); magenta, Glu41, Cys84 (residues involved in polymerization). Hydrogen atoms in Gly55 are depicted as spheres.
Extended Data Fig. 6 Genome-wide CRISPR–Cas9 screens to identify the molecular machinery involved in BI-3802-induced degradation of BCL6.
a, Schematic of the BCL6 stability reporter-based sorting screen. b, c, Genome-wide CRISPR–Cas9 knockout screen for eGFP–BCL6 stability in HEK293TCas9 cells after 16 h of treatment with 1 μM BI-3802 or DMSO. Results for SIAH1 and FBXO11 (a previously reported E3 ligase involved in BCL6 endogenous degradation) are labelled. Guides were collapsed to gene level (n = 3; four guides per gene; two-sided empirical rank-sum test-statistics). d, Normalized read counts in each sorted gate for 4 sgRNAs targeting SIAH1 and 4,000 non-targeting controls (NTC). Symbols indicate the mean normalized read numbers for each sgRNA (n = 3). e, Flow cytometry analysis of HEK293TCas9 cells expressing the full-length eGFP–BCL6 reporter and individual sgRNAs after 4 h treatment with DMSO or 1 μM BI-3802. Bars represent mean (n = 3). f, Schematic of the genome-wide CRISPR–Cas9 resistance screen. g, Genome-wide CRISPR–Cas9 knockout screen for resistance to BI-3802. Guides were collapsed to gene level (n = 3; four guides per gene; two-sided empirical rank-sum test-statistics). h, Flow cytometry analysis of SuDHL4Cas9 cells expressing sgRNAs and blue fluorescent protein (marker) treated with DMSO or 1 μM BI-3802. Lines represent measurement from each replicate (n = 3).
a, Flow cytometry analysis of HEK293TCas9 cells expressing full-length eGFP–BCL6 stability reporter and vectors expressing no-insert control, SIAH1 or SIAH1(C44S), treated with DMSO or BI-3802 for 2 h. Bars represent the mean (n = 3). b, Alignment of the BCL6 SIAH1-recognition site with previously published peptide sequences recognized by SIAH1 with inferred consensus SIAH1-binding site. c, CRISPR–Cas9 knockout screen with the Bison library for eGFP–BCL6(1–129 + 241–260) stability in HEK293TCas9 cells after 16 h of treatment with 1 μM BI-3802 or DMSO. Guides were collapsed to gene level (n = 1; four guides per gene; two-sided empirical rank-sum test-statistics). d, Flow cytometry analysis of HEK293TCas9 cells expressing eGFP–BCL6(FL) or eGFP–BCL6(FL;VSP>GSA) treated with DMSO or 1 μM BI-3802 for 7 h (bars represent mean, n = 3).
a, SDS–PAGE gel analysis of the in vitro pull-down between recombinant SIAH1(SBD) and recombinant Strep–BCL6 in the presence of BI-3802 or DMSO. Strep, strep•Tag II (n = 2). b, Titration of BCL6(241–260) peptide binding to SIAH1(SBD) using isothermal calorimetry (n = 1). c, Titration of SIAH1(SBD) binding to BCL6(5–360) using isothermal calorimetry (n = 1). d, Recombinant strep•Tag II–BCL6(5–360) was combined with full length SIAH1 and a panel of E2 enzymes (Boston Biochem) and screened for ubiquitination activity in vitro. Samples were analysed by western blot and visualized by strep•Tag II antibody–HRP conjugate (n = 1). e, Bodipy-labelled BCL6(5–360) variants (WT, E41A, Y58A) were titrated to 0.2 μM biotinylated SIAH1(SBD) in the presence of 2 μM BI-3802, and the signal was measured by TR-FRET. Dots represent mean. Lines represent standard four-parameter log-logistic curve fit (n = 3). f, Preassembled 0.2 μM Bodipy-labelled BCL6(5–360) and 0.2 μM biotinylated SIAH1(SBD) were treated with an increasing concentration of BI-3802 or BI-3812, and the signal was measured by TR-FRET. Dots represent mean. Lines represent standard four-parameter log-logistic curve fit (n = 3). g, HEK293T cells transiently transfected with nano-luciferase-tagged SIAH1(C44S) and HaloTag-labelled BCL6 constructs were treated with DMSO, 1 μM BI-3802 or 1 μM BI-3812 for 2 h and the mBRET signal was measured. Bars represent mean (n = 3). One-sided t-test. h, Preassembled 0.1 μM FITC-labelled BCoR peptide and 0.1 μM biotinylated BCL6(5–129) were treated with an increasing concentration of BI-3802 or BI-3812, and the signal was measured by TR-FRET. Lines represent standard four-parameter log-logistic curve fit (n = 3). i, HEK293TCas9 cells expressing the eGFP–BCL6(1–250) stability reporter and V5–SIAH1 were treated with 0.5 μM MLN7243 for 2 h and 1 μM BI-3802 for 1 h. Cells were imaged by indirect immunofluorescence as indicated. Scale bar, 5 μm (n = 2).
This file contains Supplementary Figure 1: Uncropped Western blots and SDS-PAGE gels, and Supplementary Figure 2: Gating strategy for flow cytometry.
Supplementary Data 1: Proteome quantification using tandem mass tag spectrometry data.
Supplementary Data 2: Functional genomics data.
Oligonucleotides used in this study.
Scripts used to analyze the proteomics, computational modeling, and functional genomic data: https://github.com/fischerlab/scripts-publications/tree/master/2020_BCL6_polymerization.
HEK293TCas9 cells expressing the eGFPBCL61–250 reporter were imaged after treatment with 1 µM BI-3802.
HEK293TCas9 cells expressing the eGFPBCL61–250 reporter were imaged after treatment with DMSO.
HEK293TCas9 cells expressing the eGFPBCL61–275 reporter were imaged after treatment with 1 µM BI-3802.
HEK293TCas9 cells expressing the eGFPBCL61–275 reporter were imaged after treatment with DMSO.
HEK293TCas9 cells expressing the eGFPBCL6FL reporter were imaged after treatment with 1 µM BI-3802.
HEK293TCas9 cells expressing the eGFPBCL6FL reporter were imaged after treatment with DMSO.
HEK293TCas9 cells expressing the eGFPBCL61–250 reporter were imaged after treatment with 1 µM BI-3802 and after 75 minutes, 10 µM BI-3812 was spiked in.
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Słabicki, M., Yoon, H., Koeppel, J. et al. Small-molecule-induced polymerization triggers degradation of BCL6. Nature (2020). https://doi.org/10.1038/s41586-020-2925-1