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Whereas oncogenes can potentially be inhibited with small molecules, the loss of tumour suppressors is more common and is problematic because the tumour-suppressor proteins are no longer present to be targeted. Notable examples include SMARCB1-mutant cancers, which are highly lethal malignancies driven by the inactivation of a subunit of SWI/SNF (also known as BAF) chromatin-remodelling complexes. Here, to generate mechanistic insights into the consequences of SMARCB1 mutation and to identify vulnerabilities, we contributed 14 SMARCB1-mutant cell lines to a near genome-wide CRISPR screen as part of the Cancer Dependency Map Project 1-3 . We report that the little-studied gene DDB1-CUL4-associated factor 5 (DCAF5) is required for the survival of SMARCB1-mutant cancers. We show that DCAF5 has a quality-control function for SWI/SNF complexes and promotes the degradation of incompletely assembled SWI/SNF complexes in the absence of SMARCB1. After depletion of DCAF5, SMARCB1-deficient SWI/SNF complexes reaccumulate, bind to target loci and restore SWI/SNF-mediated gene expression to levels that are sufficient to reverse the cancer state, including in vivo. Consequently, cancer results not from the loss of SMARCB1 function per se, but rather from DCAF5-mediated degradation of SWI/SNF complexes. These data indicate that therapeutic targeting of ubiquitin-mediated quality-control factors may effectively reverse the malignant state of some cancers driven by disruption of tumour suppressor complexes.

Titel:	Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF.
Autor/in / Beteiligte Person:	Radko-Juettner, S ; Yue, H ; Myers, JA ; Carter, RD ; Robertson, AN ; Mittal, P ; Zhu, Z ; Hansen, BS ; Donovan, KA ; Hunkeler, M ; Rosikiewicz, W ; Wu, Z ; McReynolds, MG ; Roy Burman, SS ; Schmoker, AM ; Mageed, N ; Brown, SA ; Mobley, RJ ; Partridge, JF ; Stewart, EA ; Pruett-Miller, SM ; Nabet, B ; Peng, J ; Gray, NS ; Fischer, ES ; Roberts, CWM
Link:	View record at Springer (Volltext)
Zeitschrift:	Nature, Jg. 628 (2024-04-01), Heft 8007, S. 442-449
Veröffentlichung:	Basingstoke : Nature Publishing Group ; <i>Original Publication</i>: London, Macmillan Journals ltd., 2024
Medientyp:	academicJournal
ISSN:	1476-4687 (electronic)
DOI:	10.1038/s41586-024-07250-1
Schlagwort:	Animals Female Humans Male Mice Cell Line, Tumor CRISPR-Cas Systems Gene Editing Tumor Suppressor Proteins deficiency Tumor Suppressor Proteins genetics Tumor Suppressor Proteins metabolism Proteolysis Ubiquitin metabolism Mutation Neoplasms genetics Neoplasms metabolism SMARCB1 Protein deficiency SMARCB1 Protein genetics SMARCB1 Protein metabolism Multiprotein Complexes chemistry Multiprotein Complexes metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Nature] 2024 Apr; Vol. 628 (8007), pp. 442-449. <i>Date of Electronic Publication: </i>2024 Mar 27. MeSH Terms: Mutation* ; Neoplasms* / genetics ; Neoplasms* / metabolism ; SMARCB1 Protein* / deficiency ; SMARCB1 Protein* / genetics ; SMARCB1 Protein* / metabolism ; Multiprotein Complexes* / chemistry ; Multiprotein Complexes* / metabolism ; Animals ; Female ; Humans ; Male ; Mice ; Cell Line, Tumor ; CRISPR-Cas Systems ; Gene Editing ; Tumor Suppressor Proteins / deficiency ; Tumor Suppressor Proteins / genetics ; Tumor Suppressor Proteins / metabolism ; Proteolysis ; Ubiquitin / metabolism Comments: Erratum in: Nature. 2024 Apr 29;:. (PMID: 38684813) References: Dharia, N. V. et al. A first-generation pediatric cancer dependency map. Nat. Genet. 53, 529–538 (2021). (PMID: 33753930804951710.1038/s41588-021-00819-w) ; 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). (PMID: 26780180474412510.1038/nbt.3437) ; 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). (PMID: 29083409570919310.1038/ng.3984) ; Mittal, P. & Roberts, C. W. M. The SWI/SNF complex in cancer—biology, biomarkers and therapy. Nat. Rev. Clin. Oncol. 17, 435–448 (2020). (PMID: 32303701872379210.1038/s41571-020-0357-3) ; Zhu, Z. et al. Mitotic bookmarking by SWI/SNF subunits. Nature 618, 180–187 (2023). (PMID: 372259801030308310.1038/s41586-023-06085-6) ; Wang, X. et al. SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation. Nat. Genet. 49, 289–295 (2017). (PMID: 2794179710.1038/ng.3746) ; Nakayama, R. T. et al. SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters. Nat. Genet. 49, 1613–1623 (2017). (PMID: 28945250580308010.1038/ng.3958) ; Alver, B. H. et al. The SWI/SNF chromatin remodelling complex is required for maintenance of lineage specific enhancers. Nat. Commun. 8, 14648 (2017). (PMID: 28262751534348210.1038/ncomms14648) ; Valencia, A. M. et al. Recurrent SMARCB1 mutations reveal a nucleosome acidic patch interaction site that potentiates mSWI/SNF complex chromatin remodeling. Cell 179, 1342–1356 (2019). (PMID: 31759698717541110.1016/j.cell.2019.10.044) ; Versteege, I. et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 394, 203–206 (1998). (PMID: 967130710.1038/28212) ; Lee, R. S. et al. A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers. J. Clin. Invest. 122, 2983–2988 (2012). (PMID: 22797305340875410.1172/JCI64400) ; Le Loarer, F. et al. Consistent SMARCB1 homozygous deletions in epithelioid sarcoma and in a subset of myoepithelial carcinomas can be reliably detected by FISH in archival material. Genes Chromosomes Cancer 53, 475–486 (2014). (PMID: 24585572422665010.1002/gcc.22159) ; Roberts, C. W. M., Leroux, M. M., Fleming, M. D. & Orkin, S. H. Highly penetrant, rapid tumorigenesis through conditional inversion of the tumor suppressor gene Snf5. Cancer Cell 2, 415–425 (2002). (PMID: 1245079610.1016/S1535-6108(02)00185-X) ; Leng, F. et al. Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4 DCAF5 ubiquitin ligase. Nat. Commun. 9, 1641 (2018). (PMID: 29691401591560010.1038/s41467-018-04019-9) ; Zhang, C. X. et al. Proteolysis of methylated SOX2 protein is regulated by L3MBTL3 and CRL4 DCAF5 ubiquitin ligase. J. Biol. Chem. 294, 476–489 (2019). (PMID: 3044271310.1074/jbc.RA118.005336) ; He, Y. Z. J., McCall, C. M., Hu, J., Zeng, Y. X. & Xiong, Y. DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes Dev. 20, 2949–2954 (2006). (PMID: 17079684162002510.1101/gad.1483206) ; Lee, J. & Zhou, P. DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase. Mol. Cell 26, 775–780 (2007). (PMID: 1758851310.1016/j.molcel.2007.06.001) ; Ahn, J. et al. The cullin-RING E3 ubiquitin ligase CRL4-DCAF1 complex dimerizes via a short helical region in DCAF1. Biochemistry 50, 1359–1367 (2011). (PMID: 2122647910.1021/bi101749s) ; Angers, S. et al. Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Nature 443, 590–593 (2006). (PMID: 1696424010.1038/nature05175) ; Wang, X. et al. BRD9 defines a SWI/SNF sub-complex and constitutes a specific vulnerability in malignant rhabdoid tumors. Nat. Commun. 10, 1881 (2019). (PMID: 31015438647905010.1038/s41467-019-09891-7) ; Shabek, N. et al. Structural insights into DDA1 function as a core component of the CRL4-DDB1 ubiquitin ligase. Cell Discov. 4, 67 (2018). (PMID: 30564455628812610.1038/s41421-018-0064-8) ; Li, T., Robert, E. I., van Breugel, P. C., Strubin, M. & Zheng, N. A promiscuous α-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery. Nat. Struct. Mol. Biol. 17, 105–111 (2010). (PMID: 1996679910.1038/nsmb.1719) ; Wang, X. F. et al. SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation. Cancer. Res. https://doi.org/10.1158/1538-7445.Am2017-Lb-096 (2017). ; Alpsoy, A. & Dykhuizen, E. C. Glioma tumor suppressor candidate region gene 1 (GLTSCR1) and its paralog GLTSCR1-like form SWI/SNF chromatin remodeling subcomplexes. J. Biol. Chem. 293, 3892–3903 (2018). (PMID: 29374058585800310.1074/jbc.RA117.001065) ; Michel, B. C. et al. A non-canonical SWI/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation. Nat. Cell Biol. 20, 1410–1420 (2018). (PMID: 30397315669838610.1038/s41556-018-0221-1) ; Guo, P. et al. The assembly of mammalian SWI/SNF chromatin remodeling complexes is regulated by lysine-methylation dependent proteolysis. Nat. Commun. 13, 6696 (2022). (PMID: 36335117963715810.1038/s41467-022-34348-9) ; Nabet, B. et al. Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules. Nat. Commun. 11, 4687 (2020). (PMID: 32948771750129610.1038/s41467-020-18377-w) ; Nabet, B. et al. The dTAG system for immediate and target-specific protein degradation. Nat. Chem. Biol. 14, 431–441 (2018). (PMID: 29581585629591310.1038/s41589-018-0021-8) ; Mashtalir, N. et al. Modular organization and assembly of SWI/SNF family chromatin remodeling complexes. Cell 175, 1272–1288 (2018). (PMID: 30343899679182410.1016/j.cell.2018.09.032) ; Evans, R. et al. Protein complex prediction with AlphaFold-Multimer. Preprint at bioRxiv https://doi.org/10.1101/2021.10.04.463034 (2022). ; Peng, J. et al. A proteomics approach to understanding protein ubiquitination. Nat. Biotechnol. 21, 921–926 (2003). (PMID: 1287213110.1038/nbt849) ; Langer, L. F., Ward, J. M. & Archer, T. K. Tumor suppressor SMARCB1 suppresses super-enhancers to govern hESC lineage determination. eLife 8, e45672 (2019). (PMID: 31033435653837410.7554/eLife.45672) ; Huang, Z. Q., Li, J., Sachs, L. M., Cole, P. A. & Wong, J. A role for cofactor-cofactor and cofactor-histone interactions in targeting p300, SWI/SNF and Mediator for transcription. EMBO J. 22, 2146–2155 (2003). (PMID: 1272788115609110.1093/emboj/cdg219) ; Schick, S. et al. Acute BAF perturbation causes immediate changes in chromatin accessibility. Nat. Genet. 53, 269–278 (2021). (PMID: 33558760761408210.1038/s41588-021-00777-3) ; Mashtalir, N. et al. A structural model of the endogenous human BAF complex informs disease mechanisms. Cell 183, 802–817 (2020). (PMID: 33053319771717710.1016/j.cell.2020.09.051) ; Phelan, M. L., Sif, S., Narlikar, G. J. & Kingston, R. E. Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits. Mol. Cell 3, 247–253 (1999). (PMID: 1007820710.1016/S1097-2765(00)80315-9) ; Wolf, B. K. et al. Cooperation of chromatin remodeling SWI/SNF complex and pioneer factor AP-1 shapes 3D enhancer landscapes. Nat. Struct. Mol. Biol. 30, 10–21 (2023). (PMID: 3652242610.1038/s41594-022-00880-x) ; Vierbuchen, T. et al. AP-1 transcription factors and the BAF complex mediate signal-dependent enhancer selection. Mol. Cell 68, 1067–1082 (2017). (PMID: 29272704574488110.1016/j.molcel.2017.11.026) ; Schapira, M., Tyers, M., Torrent, M. & Arrowsmith, C. H. WD40 repeat domain proteins: a novel target class? Nat. Rev. Drug Discov. 16, 773–786 (2017). (PMID: 29026209597595710.1038/nrd.2017.179) ; Grebien, F. et al. Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia. Nat. Chem. Biol. 11, 571–578 (2015). (PMID: 26167872451183310.1038/nchembio.1859) ; He, Y. P. et al. The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex. Nat. Chem. Biol. 13, 922–922 (2017). (PMID: 2885373810.1038/nchembio0817-922b) ; Qi, W. et al. An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED. Cancer Res. https://doi.org/10.1158/1538-7445.Am2017-Lb-288 (2017). ; Stewart, E. et al. Targeting the DNA repair pathway in Ewing sarcoma. Cell Rep. 9, 829–840 (2014). (PMID: 25437539438666910.1016/j.celrep.2014.09.028) ; Lord, C. J. & Ashworth, A. PARP inhibitors: Synthetic lethality in the clinic. Science 355, 1152–1158 (2017). (PMID: 28302823617505010.1126/science.aam7344) ; Brien, G. L. et al. Targeted degradation of BRD9 reverses oncogenic gene expression in synovial sarcoma. eLife 7, e41305 (2018). (PMID: 30431433627719710.7554/eLife.41305) ; Padovani, C., Jevtic, P. & Rape, M. Quality control of protein complex composition. Mol. Cell 82, 1439–1450 (2022). (PMID: 3531666010.1016/j.molcel.2022.02.029) ; Mena, E. L. et al. Dimerization quality control ensures neuronal development and survival. Science 362, eaap8236 (2018). (PMID: 3019031010.1126/science.aap8236) ; Hong, A. L. et al. Renal medullary carcinomas depend upon SMARCB1 loss and are sensitive to proteasome inhibition. eLife 8, e44161 (2019). (PMID: 30860482643689510.7554/eLife.44161) ; Helming, K. C. et al. ARID1B is a specific vulnerability in ARID1A-mutant cancers. Nat. Med. 20, 251–254 (2014). (PMID: 24562383395470410.1038/nm.3480) ; Wilson, B. G. et al. Residual complexes containing SMARCA2 (BRM) underlie the oncogenic drive of SMARCA4 (BRG1) mutation. Mol. Cell. Biol. 34, 1136–1144 (2014). (PMID: 24421395395803410.1128/MCB.01372-13) ; Wang, L., Li, L. R. & Young, K. H. New agents and regimens for diffuse large B cell lymphoma. J. Hematol. Oncol. 13, 175 (2020). (PMID: 33317571773486210.1186/s13045-020-01011-z) ; Stewart, E. et al. Targeting the DNA repair pathway in Ewing sarcoma. Cell Rep. 9, 829–841 (2014). (PMID: 25437539438666910.1016/j.celrep.2014.09.028) ; Zheng, M. et al. Caspase-6 promotes activation of the caspase-11-NLRP3 inflammasome during Gram-negative bacterial infections. J. Biol. Chem. 297, 101379 (2021). (PMID: 34740613863368710.1016/j.jbc.2021.101379) ; Sidoli, S. et al. One minute analysis of 200 histone posttranslational modifications by direct injection mass spectrometry. Genome Res. 29, 978–987 (2019). (PMID: 31123082658105110.1101/gr.247353.118) ; Drosos, Y. et al. NSD1 mediates antagonism between SWI/SNF and polycomb complexes and is required for transcriptional activation upon EZH2 inhibition. Mol. Cell 82, 2472–2489 (2022). (PMID: 35537449952060710.1016/j.molcel.2022.04.015) ; Connelly, J. P. & Pruett-Miller, S. M. CRIS.py: a versatile and high-throughput analysis program for CRISPR-based genome editing. Sci. Rep. 9, 4194 (2019). (PMID: 30862905641449610.1038/s41598-019-40896-w) ; McAlister, G. C. et al. MultiNotch MS3 enables accurate, sensitive, and multiplexed detection of differential expression across cancer cell line proteomes. Anal. Chem. 86, 7150–7158 (2014). ; Rose, C. M. et al. Highly multiplexed quantitative mass spectrometry analysis of ubiquitylomes. Cell Syst. 3, 395–403 (2016). (PMID: 27667366524107910.1016/j.cels.2016.08.009) ; Yu, K. et al. High-throughput profiling of proteome and posttranslational modifications by 16-plex TMT labeling and mass spectrometry. Methods Mol. Biol. 2228, 205–224 (2021). (PMID: 33950493845800910.1007/978-1-0716-1024-4_15) ; Faust, T. B. et al. Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15. Nat. Chem. Biol. 16, 7–14 (2020). (PMID: 3168603110.1038/s41589-019-0378-3) ; 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). (PMID: 1906185310.1016/j.ab.2008.10.044) ; He, S. et al. Structure of nucleosome-bound human BAF complex. Science 367, 875–881 (2020). (PMID: 3200152610.1126/science.aaz9761) ; Schorb, M., Haberbosch, I., Hagen, W. J. H., Schwab, Y. & Mastronarde, D. N. Software tools for automated transmission electron microscopy. Nat. Methods 16, 471–477 (2019). (PMID: 31086343700023810.1038/s41592-019-0396-9) ; Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017). (PMID: 2816547310.1038/nmeth.4169) ; Scheres, S. H. & Chen, S. Prevention of overfitting in cryo-EM structure determination. Nat. Methods 9, 853–854 (2012). (PMID: 22842542491203310.1038/nmeth.2115) ; Rosenthal, P. B. & Henderson, R. Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy. J. Mol. Biol. 333, 721–745 (2003). (PMID: 1456853310.1016/j.jmb.2003.07.013) ; Bepler, T. et al. Positive-unlabeled convolutional neural networks for particle picking in cryo-electron micrographs. Nat. Methods 16, 1153–1160 (2019). (PMID: 31591578685854510.1038/s41592-019-0575-8) ; Sanchez-Garcia, R. et al. DeepEMhancer: a deep learning solution for cryo-EM volume post-processing. Commun. Biol. 4, 874 (2021). (PMID: 34267316828284710.1038/s42003-021-02399-1) ; Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010). (PMID: 20383002285231310.1107/S0907444910007493) ; Baek, M. et al. Accurate prediction of protein structures and interactions using a three-track neural network. Science 373, 871–876 (2021). (PMID: 34282049761221310.1126/science.abj8754) ; Goddard, T. D. et al. UCSF ChimeraX: meeting modern challenges in visualization and analysis. Protein Sci. 27, 14–25 (2018). (PMID: 2871077410.1002/pro.3235) ; Croll, T. I. ISOLDE: a physically realistic environment for model building into low-resolution electron-density maps. Acta Crystallogr. D 74, 519–530 (2018). (PMID: 10.1107/S2059798318002425) ; Leman, J. K. et al. Macromolecular modeling and design in Rosetta: recent methods and frameworks. Nat. Methods 17, 665–680 (2020). (PMID: 3248333310.1038/s41592-020-0848-2) ; Wang, R. Y. et al. Automated structure refinement of macromolecular assemblies from cryo-EM maps using Rosetta. eLife 5, e17219 (2016). (PMID: 27669148511586810.7554/eLife.17219) ; Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213–221 (2010). (PMID: 20124702281567010.1107/S0907444909052925) ; Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr. D 74, 531–544 (2018). (PMID: 10.1107/S2059798318006551) ; Krissinel, E. & Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774–797 (2007). (PMID: 1768153710.1016/j.jmb.2007.05.022) ; Krissinel, E. & Henrick, K. Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions. Acta Crystallogr. D 60, 2256–2268 (2004). (PMID: 1557277910.1107/S0907444904026460) ; Armon, A., Graur, D. & Ben-Tal, N. ConSurf: an algorithmic tool for the identification of functional regions in proteins by surface mapping of phylogenetic information. J. Mol. Biol. 307, 447–463 (2001). (PMID: 1124383010.1006/jmbi.2000.4474) ; Cardone, G., Heymann, J. B. & Steven, A. C. One number does not fit all: mapping local variations in resolution in cryo-EM reconstructions. J. Struct. Biol. 184, 226–236 (2013). (PMID: 2395465310.1016/j.jsb.2013.08.002) ; Tan, Y. Z. et al. Addressing preferred specimen orientation in single-particle cryo-EM through tilting. Nat. Methods 14, 793–796 (2017). (PMID: 28671674553364910.1038/nmeth.4347) ; Morin, A. et al. Collaboration gets the most out of software. eLife 2, e01456 (2013). (PMID: 24040512377156310.7554/eLife.01456) ; Duda, D. M. et al. Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. Cell 134, 995–1006 (2008). (PMID: 18805092262863110.1016/j.cell.2008.07.022) ; Fischer, E. S. et al. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. Nature 512, 49–53 (2014). (PMID: 25043012442381910.1038/nature13527) ; Radko-Juettner, S. et al. Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF. GitHub https://github.com/jamyers2358/SWISNF.DCAF5.Dependency (2024). Substance Nomenclature: 0 (SMARCB1 Protein) ; 0 (SMARCB1 protein, human) ; 0 (Tumor Suppressor Proteins) ; 0 (Multiprotein Complexes) ; 0 (Ubiquitin) Entry Date(s): Date Created: 20240328 Date Completed: 20240412 Latest Revision: 20240429 Update Code: 20240430

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Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF.