Mapping the IMiD-dependent cereblon interactome using BioID-proximity labelling.
BioID2
IMiDs
bortezomib
cereblon
myosin
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
08 Jul 2024
08 Jul 2024
Historique:
revised:
17
04
2024
received:
03
12
2023
accepted:
24
05
2024
medline:
8
7
2024
pubmed:
8
7
2024
entrez:
8
7
2024
Statut:
aheadofprint
Résumé
Immunomodulatory imide drugs (IMiDs) are central components of therapy for multiple myeloma (MM). IMiDs bind cereblon (CRBN), an adaptor for the CUL4-DDB1-RBX1 E3 ligase to change its substrate specificity and induce degradation of 'neosubstrate' transcription factors that are essential to MM cells. Mechanistic studies to date have largely focussed on mediators of therapeutic activity and insight into clinical IMiD toxicities is less developed. We adopted BioID2-dependent proximity labelling (BioID2-CRBN) to characterise the CRBN interactome in the presence and absence of various IMiDs and the proteasome inhibitor, bortezomib. We aimed to leverage this technology to further map CRBN interactions beyond what has been achieved by conventional proteomic techniques. In support of this approach, analysis of cells expressing BioID2-CRBN following IMiD treatment displayed biotinylation of known CRBN interactors and neosubstrates. We observed that bortezomib alone significantly modifies the CRBN interactome. Proximity labelling also suggested that IMiDs augment the interaction between CRBN and proteins that are not degraded, thus designating 'neointeractors' distinct from previously disclosed 'neosubstrates'. Here we identify Non-Muscle Myosin Heavy Chain IIA (MYH9) as a putative CRBN neointeractor that may contribute to the haematological toxicity of IMiDs. These studies provide proof of concept for proximity labelling technologies in the mechanistic profiling of IMiDs and related E3-ligase-modulating drugs.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Family of Mr Lawrence Bode
Organisme : National Health and Medical Research Council
ID : GNT2009177
Organisme : Monash Haematology Research Grant
Informations de copyright
© 2024 The Author(s). The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Références
Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA et al. (2008) Improved survival in multiple myeloma and the impact of novel therapies. Blood 111, 2516–2520.
Gooding S, Ansari‐Pour N, Towfic F, Estévez MO, Chamberlain PP, Tsai KT, Flynt E, Hirst M, Rozelle D, Dhiman P et al. (2021) Multiple cereblon genetic changes are associated with acquired resistance to lenalidomide or pomalidomide in multiple myeloma. Blood 137, 232–237.
Kortüm KM, Mai EK, Hanafiah NH, Shi C‐X, Zhu Y‐X, Bruins L, Barrio S, Jedlowski P, Merz M et al. (2016) Targeted sequencing of refractory myeloma reveals a high incidence of mutations in CRBN and Ras pathway genes. Blood 128, 1226–1233.
Ghobrial IM & Rajkumar SV (2003) Management of thalidomide toxicity. J Support Oncol 1, 194–205.
Mateos M‐V, García‐Sanz R, Colado E, Olazábal J & San‐Miguel J (2008) Should prophylactic granulocyte‐colony stimulating factor be used in multiple myeloma patients developing neutropenia under lenalidomide‐based therapy? Br J Haematol 140, 324–326.
Palumbo A, Falco P, Corradini P, Falcone A, Di Raimondo F, Giuliani N, Crippa C, Ciccone G, Omedè P, Ambrosini MT et al. (2007) Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA—Italian Multiple Myeloma Network. J Clin Oncol 25, 4459–4465.
Hirsh J (2007) Risk of thrombosis with lenalidomide and its prevention with aspirin. Chest 131, 275–277.
Krönke J, Udeshi ND, Narla A, Grauman P, Hurst SN, McConkey M, Svinkina T, Heckl D, Comer E, Li X et al. (2014) Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science 343, 301–305.
Lu G, Middleton RE, Sun H, Naniong M, Ott CJ, Mitsiades CS, Wong K‐K, Bradner JE & Kaelin WG (2014) The myeloma drug Lenalidomide promotes the cereblon‐dependent destruction of Ikaros proteins. Science 343, 305–309.
Sievers QL, Gasser JA, Cowley GS, Fischer ES & Ebert BL (2018) Genome‐wide screen identifies cullin‐RING ligase machinery required for lenalidomide‐dependent CRL4CRBN activity. Blood 132, 1293–1303.
Liu J, Song T, Zhou W, Xing L, Wang S, Ho M, Peng Z, Tai Y‐T, Hideshima T, Anderson KC et al. (2019) A genome‐scale CRISPR‐Cas9 screening in myeloma cells identifies regulators of immunomodulatory drug sensitivity. Leukemia 33, 171–180.
Chen Y‐A, Peng Y‐J, Hu M‐C, Huang J‐J, Chien Y‐C, Wu J‐T, Chen T‐Y & Tang C‐Y (2015) The Cullin 4A/B‐DDB1‐cereblon E3 ubiquitin ligase complex mediates the degradation of CLC‐1 chloride channels. Sci Rep 5, 10667.
Tateno S, Iida M, Fujii S, Suwa T, Katayama M, Tokuyama H, Yamamoto J, Ito T, Sakamoto S, Handa H et al. (2020) Genome‐wide screening reveals a role for subcellular localization of CRBN in the anti‐myeloma activity of pomalidomide. Sci Rep 10, 4012.
Costacurta M, Vervoort SJ, Hogg SJ, Martin BP, Johnstone RW & Shortt J (2021) Whole genome CRISPR screening identifies TOP2B as a potential target for IMiD sensitization in multiple myeloma. Haematologica 106, 2013–2017.
Van Nguyen T, Lee JE, Sweredoski MJ, Yang SJ, Jeon S‐J, Harrison JS, Yim J‐H, Lee SG, Handa H, Kuhlman B et al. (2016) Glutamine triggers acetylation‐dependent degradation of glutamine synthetase via the thalidomide receptor cereblon. Mol Cell 61, 809–820.
Lu G, Weng S, Matyskiela M, Zheng X, Fang W, Wood S, Surka C, Mizukoshi R, Lu C‐C, Mendy D et al. (2018) UBE2G1 governs the destruction of cereblon neomorphic substrates. Elife 7, e40958.
Sebastian S, Zhu YX, Braggio E, Shi C‐X, Panchabhai SC, Van Wier SA, Ahmann GJ, Chesi M, Bergsagel PL, Stewart AK et al. (2017) Multiple myeloma cells' capacity to decompose H2O2 determines lenalidomide sensitivity. Blood 129, 991–1007.
Eichner R, Heider M, Fernández‐Sáiz V, van Bebber F, Garz A‐K, Lemeer S, Rudelius M, Targosz B‐S, Jacobs L, Knorn A‐M et al. (2016) Immunomodulatory drugs disrupt the cereblon–CD147–MCT1 axis to exert antitumor activity and teratogenicity. Nat Med 22, 735–743.
Heider M, Eichner R, Stroh J, Morath V, Kuisl A, Zecha J, Lawatscheck J, Baek K, Garz A‐K, Rudelius M et al. (2021) The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma. Mol Cell 81, 1170–1186.e10.
Costacurta M, He J, Thompson PE & Shortt J (2021) Molecular mechanisms of cereblon‐interacting small molecules in multiple myeloma therapy. J Pers Med 11, 1185.
Roux KJ, Kim DI, Raida M & Burke B (2012) A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells. J Cell Biol 196, 801–810.
Roux KJ, Kim DI, Burke B & May DG (2018) BioID: a screen for protein‐protein interactions. Curr Protoc Protein Sci 91, 19.23.1–19.23.15.
Kim DI, Jensen SC, Noble KA, Kc B, Roux KH, Motamedchaboki K & Roux KJ (2016) An improved smaller biotin ligase for BioID proximity labeling. Mol Biol Cell 27, 1188–1196.
Yamanaka S, Horiuchi Y, Matsuoka S, Kido K, Nishino K, Maeno M, Shibata N, Kosako H & Sawasaki T (2022) A proximity biotinylation‐based approach to identify protein‐E3 ligase interactions induced by PROTACs and molecular glues. Nat Commun 13, 183.
Pecci A, Ma X, Savoia A & Adelstein RS (2018) MYH9: structure, functions and role of non‐muscle myosin IIA in human disease. Gene 664, 152–167.
Asensio‐Juárez G, Llorente‐González C & Vicente‐Manzanares M (2020) Linking the landscape of MYH9‐related diseases to the molecular mechanisms that control non‐muscle myosin II‐A function in cells. Cells 9, 1458.
Vicente‐Manzanares M, Ma X, Adelstein RS & Horwitz AR (2009) Non‐muscle myosin II takes centre stage in cell adhesion and migration. Nat Rev Mol Cell Biol 10, 778–790.
Li X & Song Y (2020) Proteolysis‐targeting chimera (PROTAC) for targeted protein degradation and cancer therapy. J Hematol Oncol 13, 50.
Sievers QL, Petzold G, Bunker RD, Renneville A, Słabicki M, Liddicoat BJ, Abdulrahman W, Mikkelsen T, Ebert BL & Thomä NH (2018) Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN. Science 362, eaat0572.
Dunbar K, Macartney TJ & Sapkota GP (2021) IMiDs induce FAM83F degradation via an interaction with CK1α to attenuate Wnt signalling. Life Sci Alliance 4, e202000804.
Krönke J, Fink EC, Hollenbach PW, MacBeth KJ, Hurst SN, Udeshi ND, Chamberlain PP, Mani DR, Man HW, Gandhi AK et al. (2015) Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS. Nature 523, 183–188.
Lonial S, van de Donk NWCJ, Popat R, Zonder JA, Minnema MC, Larsen J, Nguyen TV, Chen MS, Bensmaine A, Cota M et al. (2019) First clinical (phase 1b/2a) study of iberdomide (CC‐220; IBER), a CELMoD, in combination with dexamethasone (DEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol 37 supp, 8006.
Akber U, Jo H, Jeon S, Yang SJ, Bong S, Lim S, Kim YK, Park ZY & Park CS (2021) Cereblon regulates the proteotoxicity of tau by tuning the chaperone activity of DNAJA1. J Neurosci 41, 5138–5156.
Gano JJ & Simon JA (2010) A proteomic investigation of ligand‐dependent HSP90 complexes reveals CHORDC1 as a novel ADP‐dependent HSP90‐interacting protein. Mol Cell Proteomics 9, 255–270.
Liu W, Lu Y, Yan X, Lu Q, Sun Y, Wan X, Li Y, Zhao J, Li Y & Jiang G (2022) Current understanding on the role of CCT3 in cancer research. Front Oncol 12, 961733.
Fournier MJ, Gareau C & Mazroui R (2010) The chemotherapeutic agent bortezomib induces the formation of stress granules. Cancer Cell Int 10, 12.
Marcelo A, Koppenol R, de Almeida LP, Matos CA & Nóbrega C (2021) Stress granules, RNA‐binding proteins and polyglutamine diseases: too much aggregation? Cell Death Dis 12, 592.
Mazroui R, Di Marco S, Kaufman RJ & Gallouzi I‐E (2007) Inhibition of the ubiquitin‐proteasome system induces stress granule formation. Mol Biol Cell 18, 2603–2618.
Fischer ES, Böhm K, Lydeard JR, Yang H, Stadler MB, Cavadini S, Nagel J, Serluca F, Acker V, Lingaraju GM et al. (2014) Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide. Nature 512, 49–53.
Liu J, Liu Z, Yan W, Yang H, Fang S, Deng S, Wen Y, Shen P, Li Y, Hou R et al. (2022) ENKUR recruits FBXW7 to ubiquitinate and degrade MYH9 and further suppress MYH9‐induced deubiquitination of β‐catenin to block gastric cancer metastasis. MedComm 3, e185.
Yamamoto Y, Chino H, Tsukamoto S, Ode KL, Ueda HR & Mizushima N (2021) NEK9 regulates primary cilia formation by acting as a selective autophagy adaptor for MYH9/myosin IIA. Nat Commun 12, 3292.
Ye Y & Rape M (2009) Building ubiquitin chains: E2 enzymes at work. Nat Rev Mol Cell Biol 10, 755–764.
Althaus K & Greinacher A (2009) MYH9‐related platelet disorders. Semin Thromb Hemost 35, 189–203.
Kelley MJ, Jawien W, Ortel TL & Korczak JF (2000) Mutation of MYH9, encoding non‐muscle myosin heavy chain A, in May‐Hegglin anomaly. Nat Genet 26, 106–108.
Kurochkina N & Guha U (2013) SH3 domains: modules of protein‐protein interactions. Biophys Rev 5, 29–39.
Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, Miguel JS, Barlogie B, Harousseau J, Zonder JA, Cavo M, Zangari M et al. (2008) Prevention of thalidomide‐ and lenalidomide‐associated thrombosis in myeloma. Leukemia 22, 414–423.
Girolamo A, Vettore S, Bonamigo E & Fabris F (2011) Thrombotic events in MYH9 gene‐related autosomal macrothrombocytopenias (old May‐Hegglin, Sebastian, Fechtner and Epstein syndromes). J Thromb Thrombolysis 32, 474–477.
Tochigi T, Miyamoto T, Hatakeyama K, Sakoda T, Ishihara D, Irifune H, Shima T, Kato K, Maeda T, Ito T et al. (2020) Aromatase is a novel neosubstrate of cereblon responsible for immunomodulatory drug–induced thrombocytopenia. Blood 135, 2146–2158.
Pal R, Monaghan SA, Hassett AC, Mapara MY, Schafer P, Roodman GD, Ragni MV, Moscinski L, List A & Lentzsch S (2010) Immunomodulatory derivatives induce PU.1 down‐regulation, myeloid maturation arrest, and neutropenia. Blood 115, 605–614.
Xu Y, Li J, Ferguson GD, Mercurio F, Khambatta G, Morrison L, Lopez‐Girona A, Corral LG, Webb DR, Bennett BL et al. (2009) Immunomodulatory drugs reorganize cytoskeleton by modulating rho GTPases. Blood 114, 338–345.
Fionda C, Stabile H, Molfetta R, Kosta A, Peruzzi G, Ruggeri S, Zingoni A, Capuano C, Soriani A, Paolini R et al. (2021) Cereblon regulates NK cell cytotoxicity and migration via Rac1 activation. Eur J Immunol 51, 2607–2617.
Lagrue K, Carisey A, Morgan DJ, Chopra R & Davis DM (2015) Lenalidomide augments actin remodeling and lowers NK‐cell activation thresholds. Blood 126, 50–60.
Lord SJ, Velle KB, Dyche Mullins R & Fritz‐Laylin LK (2020) SuperPlots: communicating reproducibility and variability in cell biology. J Cell Biol 219, e202001064.
Plubell DL, Wilmarth PA, Zhao Y, Fenton AM, Minnier J, Reddy AP, Klimek J, Yang X, David LL & Pamir N (2017) Extended multiplexing of tandem mass tags (TMT) labeling reveals age and high fat diet specific proteome changes in mouse epididymal adipose tissue. Mol Cell Proteomics 16, 873–890.
Robinson MD & Oshlack A (2010) A scaling normalization method for differential expression analysis of RNA‐seq data. Genome Biol 11, R25.
Robinson MD, McCarthy DJ & Smyth GK (2009) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140.
Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta‐Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP et al. (2015) STRING v10: protein‐protein interaction networks, integrated over the tree of life. Nucleic Acids Res 43, D447–D452.
Hulsen T, de Vlieg J & Alkema W (2008) BioVenn – a web application for the comparison and visualization of biological lists using area‐proportional Venn diagrams. BMC Genomics 9, 488.
Chen J, Bardes EE, Aronow BJ & Jegga AG (2009) ToppGene suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res 37, W305–311.