Controlled perturbation of protein activity is essential to study protein function in cells and living organisms. Small molecules that hijack the cellular protein ubiquitination machinery to selectively degrade proteins of interest, so-called degraders, have recently emerged as alternatives to selective chemical inhibitors, both as therapeutic modalities and as powerful research tools. These systems offer unprecedented temporal and spatial control over protein function. Here, we review recent developments in this field, with a particular focus on the use of degraders as research tools to interrogate complex biological problems.
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Ciechanover, A. Intracellular protein degradation: from a vague idea, through the lysosome and the ubiquitin-proteasome system, and onto human diseases and drug targeting (Nobel lecture). Angew. Chem. Int. Ed. Engl. 44, 5944–5967 (2005).
Dikic, I. Proteasomal and autophagic degradation systems. Annu. Rev. Biochem. 86, 193–224 (2017).
Zheng, N. & Shabek, N. Ubiquitin ligases: structure, function, and regulation. Annu. Rev. Biochem. 86, 129–157 (2017).
King, R. W., Glotzer, M. & Kirschner, M. W. Mutagenic analysis of the destruction signal of mitotic cyclins and structural characterization of ubiquitinated intermediates. Mol. Biol. Cell 7, 1343–1357 (1996).
Takeuchi, J., Chen, H., Hoyt, M. A. & Coffino, P. Structural elements of the ubiquitin-independent proteasome degron of ornithine decarboxylase. Biochem. J. 410, 401–407 (2008).
Park, E. C., Finley, D. & Szostak, J. W. A strategy for the generation of conditional mutations by protein destabilization. Proc. Natl Acad. Sci. USA 89, 1249–1252 (1992).
Pfaff, P., Samarasinghe, K. T. G., Crews, C. M. & Carreira, E. M. Reversible spatiotemporal control of induced protein degradation by bistable photoPROTACs. ACS Cent. Sci. 5, 1682–1690 (2019).
Martin, R. et al. PHOTACs enable optical control of protein degradation. Sci. Adv. 6, eaay5064 (2020).
Renicke, C., Schuster, D., Usherenko, S., Essen, L.-O. & Taxis, C. A LOV2 domain-based optogenetic tool to control protein degradation and cellular function. Chem. Biol. 20, 619–626 (2013).
Caussinus, E., Kanca, O. & Affolter, M. Fluorescent fusion protein knockout mediated by anti-GFP nanobody. Nat. Struct. Mol. Biol. 19, 117–121 (2012). This paper describes the engineering of a nanobody-based CRL substrate receptor for the degradation of GFP-fusion proteins.
Chung, H. K. et al. Tunable and reversible drug control of protein production via a self-excising degron. Nat. Chem. Biol. 11, 713–720 (2015).
Banaszynski, L. A., Chen, L. C., Maynard-Smith, L. A., Ooi, A. G. & Wandless, T. J. A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules. Cell 126, 995–1004 (2006).
Nishimura, K., Fukagawa, T., Takisawa, H., Kakimoto, T. & Kanemaki, M. An auxin-based degron system for the rapid depletion of proteins in nonplant cells. Nat. Methods 6, 917–922 (2009).
Koduri, V. et al. Peptidic degron for IMiD-induced degradation of heterologous proteins. Proc. Natl Acad. Sci. USA 116, 2539–2544 (2019).
Nabet, B. et al. The dTAG system for immediate and target-specific protein degradation. Nat. Chem. Biol. 14, 431–441 (2018). This work describes the dTAG system and demonstrates its utility in target validation by degrading KRAS G12V.
Buckley, D. L. et al. HaloPROTACS: use of small molecule PROTACs to induce degradation of HaloTag fusion proteins. ACS Chem. Biol. 10, 1831–1837 (2015). This paper describes the development of HaloPROTAC for the degradation of Halo-tagged proteins.
Sakamoto, K. M. et al. Protacs: chimeric molecules that target proteins to the Skp1–Cullin–F box complex for ubiquitination and degradation. Proc. Natl Acad. Sci. USA 98, 8554–8559 (2001). This paper shows the first example of using chimeric molecules to redirect the specificity of a ubiquitin ligase toward a target protein of interest.
Gray, W. M., Kepinski, S., Rouse, D., Leyser, O. & Estelle, M. Auxin regulates SCF(TIR1)-dependent degradation of AUX/IAA proteins. Nature 414, 271–276 (2001).
Pettersson, M. & Crews, C. M. PROteolysis TArgeting Chimeras (PROTACs)—past, present and future. Drug Discov. Today Technol. 31, 15–27 (2019).
Churcher, I. Protac-induced protein degradation in drug discovery: breaking the rules or just making new ones? J. Med. Chem. 61, 444–452 (2018).
Watt, G. F., Scott-Stevens, P. & Gaohua, L. Targeted protein degradation in vivo with Proteolysis Targeting Chimeras: current status and future considerations. Drug Discov. Today Technol. 31, 69–80 (2019).
Burslem, G. M. & Crews, C. M. Small-molecule modulation of protein homeostasis. Chem. Rev. 117, 11269–11301 (2017).
Salami, J. & Crews, C. M. Waste disposal—an attractive strategy for cancer therapy. Science 355, 1163–1167 (2017).
Bondeson, D. P. et al. Catalytic in vivo protein knockdown by small-molecule PROTACs. Nat. Chem. Biol. 11, 611–617 (2015).
Lu, J. et al. Hijacking the E3 ubiquitin ligase cereblon to efficiently target BRD4. Chem. Biol. 22, 755–763 (2015).
Winter, G. E. et al. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science 348, 1376–1381 (2015).
Krönke, J. et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science 343, 301–305 (2014). This study and the concurrent study by Lu et al. (ref. 28) demonstrate how thalidomide promotes degradation of IKZF1/3 transcription factors.
Lu, G. et al. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science 343, 305–309 (2014). This study and the concurrent study by Krönke et al. (ref. 27) demonstrate how thalidomide promotes degradation of IKZF1/3 transcription factors.
Krönke, J., Hurst, S. N. & Ebert, B. L. Lenalidomide induces degradation of IKZF1 and IKZF3. Oncoimmunology 3, e941742 (2014).
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).
Matyskiela, M. E. et al. A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase. Nature 535, 252–257 (2016).
Donovan, K. A. et al. Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. Elife 7, e38430 (2018).
Ito, T. et al. Identification of a primary target of thalidomide teratogenicity. Science 327, 1345–1350 (2010). This study identified cereblon as a target of thalidomide.
Tan, X. et al. Mechanism of auxin perception by the TIR1 ubiquitin ligase. Nature 446, 640–645 (2007). This paper provides the structural basis for auxin perception, the first proof-of-principle study for a ‘molecular glue’ regulatory mechanism.
Faust, T. B. et al. Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15. Nat. Chem. Biol. 16, 7–14 (2020).
Bussiere, D. E. et al. Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex. Nat. Chem. Biol. 16, 15–23 (2020).
Du, X. et al. Structural basis and kinetic pathway of RBM39 recruitment to DCAF15 by a sulfonamide molecular glue E7820. Structure 27, 1625–1633.e3 (2019).
Ting, T. C. et al. Aryl sulfonamides degrade RBM39 and RBM23 by recruitment to CRL4-DCAF15. Cell Rep. 29, 1499–1510.e6 (2019).
Sheard, L. B. et al. Jasmonate perception by inositol-phosphate-potentiated COI1–JAZ co-receptor. Nature 468, 400–405 (2010).
Sievers, Q. L. et al. Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN. Science 362, eaat0572 (2018).
Huang, H.-T. et al. A chemoproteomic approach to query the degradable kinome using a multi-kinase degrader. Cell Chem. Biol. 25, 88–99.e6 (2018).
Bondeson, D. P. et al. Lessons in PROTAC design from selective degradation with a promiscuous warhead. Cell Chem. Biol. 25, 78–87.e5 (2018).
Nowak, R. P. et al. Plasticity in binding confers selectivity in ligand-induced protein degradation. Nat. Chem. Biol. 14, 706–714 (2018).
Gadd, M. S. et al. Structural basis of PROTAC cooperative recognition for selective protein degradation. Nat. Chem. Biol. 13, 514–521 (2017).
Farnaby, W. et al. BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design. Nat. Chem. Biol. 15, 672–680 (2019).
Pozo, J. C., Timpte, C., Tan, S., Callis, J. & Estelle, M. The ubiquitin-related protein RUB1 and auxin response in. Arabidopsis. Science 280, 1760–1763 (1998).
Schwechheimer, C. et al. Interactions of the COP9 signalosome with the E3 ubiquitin ligase SCFTIR1 in mediating auxin response. Science 292, 1379–1382 (2001).
D’Amato, R. J., Loughnan, M. S., Flynn, E. & Folkman, J. Thalidomide is an inhibitor of angiogenesis. Proc. Natl Acad. Sci. USA 91, 4082–4085 (1994).
Pan, B. & Lentzsch, S. The application and biology of immunomodulatory drugs (IMiDs) in cancer. Pharmacol. Ther. 136, 56–68 (2012).
Teo, S. et al. Thalidomide in the treatment of leprosy. Microbes Infect. 4, 1193–1202 (2002).
Thomas, D. A. & Kantarjian, H. M. Current role of thalidomide in cancer treatment. Curr. Opin. Oncol. 12, 564–573 (2000).
An, J. et al. pSILAC mass spectrometry reveals ZFP91 as IMiD-dependent substrate of the CRL4CRBN ubiquitin ligase. Nat. Commun. 8, 15398 (2017).
Gandhi, A. K. et al. Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4CRBN. Br. J. Haematol. 164, 811–821 (2014).
Li, Y. et al. In vivo assessment of the effect of CYP1A2 inhibition and induction on pomalidomide pharmacokinetics in healthy subjects. J. Clin. Pharmacol. 58, 1295–1304 (2018).
Chen, N., Zhou, S. & Palmisano, M. Clinical pharmacokinetics and pharmacodynamics of lenalidomide. Clin. Pharmacokinet. 56, 139–152 (2017).
Fink, E. C. et al. Crbn I391V is sufficient to confer in vivo sensitivity to thalidomide and its derivatives in mice. Blood 132, 1535–1544 (2018).
Uehara, T. et al. Selective degradation of splicing factor CAPERα by anticancer sulfonamides. Nat. Chem. Biol. 13, 675–680 (2017). This paper and the concurrent study by Han et al. (ref. 58) demonstrate how aryl-sulfonamides promote degradation of RBM39.
Han, T. et al. Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science 356, eaal3755 (2017). This paper and the concurrent study by Uehara et al. (ref. 57) demonstrate how aryl-sulfonamides promote degradation of RBM39.
Jia, X. et al. pSILAC method coupled with two complementary digestion approaches reveals PRPF39 as a new E7070-dependent DCAF15 substrate. J. Proteomics 210, 103545 (2020).
Fischer, E. S. et al. Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide. Nature 512, 49–53 (2014).
Buckley, D. L. et al. Targeting the von Hippel–Lindau E3 ubiquitin ligase using small molecules to disrupt the VHL/HIF-1α interaction. J. Am. Chem. Soc. 134, 4465–4468 (2012).
Itoh, Y., Ishikawa, M., Naito, M. & Hashimoto, Y. Protein knockdown using methyl bestatin−ligand hybrid molecules: design and synthesis of inducers of ubiquitination-mediated degradation of cellular retinoic acid-binding proteins. J. Am. Chem. Soc. 132, 5820–5826 (2010).
Hines, J., Lartigue, S., Dong, H., Qian, Y. & Crews, C. M. MDM2-recruiting PROTAC offers superior, synergistic antiproliferative activity via simultaneous degradation of BRD4 and stabilization of p53. Cancer Res. 79, 251–262 (2019).
Zhang, X., Crowley, V. M., Wucherpfennig, T. G., Dix, M. M. & Cravatt, B. F. Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16. Nat. Chem. Biol. 15, 737–746 (2019).
Spradlin, J. N. et al. Harnessing the anticancer natural product nimbolide for targeted protein degradation. Nat. Chem. Biol. 15, 747–755 (2019).
Ward, C. C. et al. Covalent ligand screening uncovers a RNF4 E3 ligase recruiter for targeted protein degradation applications. ACS Chem. Biol. 14, 2430–2440 (2019).
Burslem, G. M., Song, J., Chen, X., Hines, J. & Crews, C. M. Enhancing antiproliferative activity and selectivity of a FLT-3 inhibitor by proteolysis targeting chimera conversion. J. Am. Chem. Soc. 140, 16428–16432 (2018).
Burslem, G. M. et al. The advantages of targeted protein degradation over inhibition: an RTK case study. Cell Chem. Biol. 25, 67–77.e3 (2018).
Li, W. et al. Phthalimide conjugations for the degradation of oncogenic PI3K. Eur. J. Med. Chem. 151, 237–247 (2018).
Tinworth, C. P. et al. PROTAC-mediated degradation of Bruton’s tyrosine kinase is inhibited by covalent binding. ACS Chem. Biol. 14, 342–347 (2019).
Salami, J. et al. Androgen receptor degradation by the proteolysis-targeting chimera ARCC-4 outperforms enzalutamide in cellular models of prostate cancer drug resistance. Commun. Biol. 1, 100 (2018).
Yang, K. et al. Development of the first small molecule histone deacetylase 6 (HDAC6) degraders. Bioorg. Med. Chem. Lett. 28, 2493–2497 (2018).
Bassi, Z. I. et al. Modulating PCAF/GCN5 immune cell function through a PROTAC approach. ACS Chem. Biol. 13, 2862–2867 (2018).
Brand, M. et al. Homolog-selective degradation as a strategy to probe the function of CDK6 in AML. Cell Chem. Biol. 26, 300–306.e9 (2019).
Jiang, B. et al. Development of dual and selective degraders of cyclin-dependent kinases 4 and 6. Angew. Chem. Int. Ed. Engl. 58, 6321–6326 (2019).
Chessum, N. E. A. et al. Demonstrating in-cell target engagement using a pirin protein degradation probe (CCT367766). J. Med. Chem. 61, 918–933 (2018).
Liu, J. et al. Light-induced control of protein destruction by opto-PROTAC. Sci. Adv. 6, eaay5154 (2020).
Xue, G., Wang, K., Zhou, D., Zhong, H. & Pan, Z. Light-induced protein degradation with photocaged PROTACs. J. Am. Chem. Soc. 141, 18370–18374 (2019).
Naro, Y., Darrah, K. & Deiters, A. Optical control of small molecule-induced protein degradation. J. Am. Chem. Soc. 142, 2193–2197 (2020).
Jin, Y. et al. Azo-PROTAC: novel light-controlled small-molecule tool for protein knockdown. J. Med. Chem. 63, 4644–4654 (2020).
Zeng, M. et al. Exploring targeted degradation strategy for oncogenic KRASG12C. Cell Chem. Biol. 27, 19–31.e6 (2020).
Li, S., Prasanna, X., Salo, V. T., Vattulainen, I. & Ikonen, E. An efficient auxin-inducible degron system with low basal degradation in human cells. Nat. Methods 16, 866–869 (2019).
Madeira da Silva, L., Owens, K. L., Murta, S. M. F. & Beverley, S. M. Regulated expression of the Leishmania major surface virulence factor lipophosphoglycan using conditionally destabilized fusion proteins. Proc. Natl Acad. Sci. USA 106, 7583–7588 (2009).
Armstrong, C. M. & Goldberg, D. E. An FKBP destabilization domain modulates protein levels in Plasmodium falciparum. Nat. Methods 4, 1007–1009 (2007).
An, W. et al. Engineering FKBP-based destabilizing domains to build sophisticated protein regulation systems. PLoS ONE 10, e0145783 (2015).
Huang, H. T. et al. MELK is not necessary for the proliferation of basal-like breast cancer cells. Elife 6, e26693 (2017).
Erb, M. A. et al. Transcription control by the ENL YEATS domain in acute leukaemia. Nature 543, 270–274 (2017).
Neklesa, T. K. et al. Small-molecule hydrophobic tagging-induced degradation of HaloTag fusion proteins. Nat. Chem. Biol. 7, 538–543 (2011).
Raina, K. et al. Targeted protein destabilization reveals an estrogen-mediated ER stress response. Nat. Chem. Biol. 10, 957–962 (2014).
Los, G. V. et al. HaloTag: a novel protein labeling technology for cell imaging and protein analysis. ACS Chem. Biol. 3, 373–382 (2008).
Tomoshige, S., Naito, M., Hashimoto, Y. & Ishikawa, M. Degradation of HaloTag-fused nuclear proteins using bestatin-HaloTag ligand hybrid molecules. Org. Biomol. Chem. 13, 9746–9750 (2015).
Tovell, H. et al. Rapid and reversible knockdown of endogenously tagged endosomal proteins via an optimized HaloPROTAC degrader. ACS Chem. Biol. 14, 882–892 (2019).
BasuRay, S., Wang, Y., Smagris, E., Cohen, J. C. & Hobbs, H. H. Accumulation of PNPLA3 on lipid droplets is the basis of associated hepatic steatosis. Proc. Natl Acad. Sci. USA 116, 9521–9526 (2019).
Shin, Y. J. et al. Nanobody-targeted E3-ubiquitin ligase complex degrades nuclear proteins. Sci. Rep. 5, 14269 (2015).
Clift, D. et al. A method for the acute and rapid degradation of endogenous proteins. Cell 171, 1692–1706.e18 (2017).
Chen, X. et al. Degradation of endogenous proteins and generation of a null-like phenotype in zebrafish using Trim-Away technology. Genome Biol. 20, 19 (2019).
Banik, S., Pedram, K., Wisnovsky, S., Riley, N. & Bertozzi, C. Lysosome targeting chimeras (LYTACs) for the degradation of secreted and membrane proteins. Preprint available at chemRxiv https://doi.org/10.26434/chemrxiv.7927061.v2 (2019). This paper shows the method of using chimeric macromolecular conjugates to target proteins for degradation by the lysosomal pathway.
Fan, X., Jin, W. Y., Lu, J., Wang, J. & Wang, Y. T. Rapid and reversible knockdown of endogenous proteins by peptide-directed lysosomal degradation. Nat. Neurosci. 17, 471–480 (2014).
Li, W. et al. Chaperone-mediated autophagy: advances from bench to bedside. Neurobiol. Dis. 122, 41–48 (2019).
Riching, K. M. et al. Quantitative live-cell kinetic degradation and mechanistic profiling of PROTAC mode of action. ACS Chem. Biol. 13, 2758–2770 (2018).
Takahashi, D. et al. AUTACs: cargo-specific degraders using selective autophagy. Mol. Cell 76, 797–810.e10 (2019). This paper shows the first examples of small molecule degraders that target proteins to the lysosomal pathway for degradation.
Matyskiela, M. E. et al. SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate. Nat. Chem. Biol. 14, 981–987 (2018).
Hagner, P. R. et al. CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL. Blood 126, 779–789 (2015).
Matyskiela, M. E. et al. A cereblon modulator (CC-220) with improved degradation of Ikaros and Aiolos. J. Med. Chem. 61, 535–542 (2018).
Gemechu, Y. et al. Humanized cereblon mice revealed two distinct therapeutic pathways of immunomodulatory drugs. Proc. Natl Acad. Sci. USA 115, 11802–11807 (2018).
Nakazawa, N., Arakawa, O. & Yanagida, M. Condensin locates at transcriptional termination sites in mitosis, possibly releasing mitotic transcripts. Open Biol. 9, 190125 (2019).
Yoshiba, S. et al. HsSAS-6-dependent cartwheel assembly ensures stabilization of centriole intermediates. J. Cell Sci. 132, jcs217521 (2019).
Goto, H. et al. Chk1-mediated Cdc25A degradation as a critical mechanism for normal cell cycle progression. J. Cell Sci. 132, jcs223123 (2019).
Boija, A. et al. Transcription factors activate genes through the phase-separation capacity of their activation domains. Cell 175, 1842–1855.e16 (2018).
Brunetti, L. et al. Mutant NPM1 maintains the leukemic state through HOX expression. Cancer Cell 34, 499–512.e9 (2018).
Fay, E. J. et al. Engineered small-molecule control of influenza A virus replication. J. Virol. 93, e01677–18 (2019).
Rago, F. et al. Degron mediated BRM/SMARCA2 depletion uncovers novel combination partners for treatment of BRG1/SMARCA4-mutant cancers. Biochem. Biophys. Res. Commun. 508, 109–116 (2019).
Zhu, W. et al. Precisely controlling endogenous protein dosage in hPSCs and derivatives to model FOXG1 syndrome. Nat. Commun. 10, 928 (2019).
Wu, Y., Yang, L., Chang, T., Kandeel, F. & Yee, J.-K. A small molecule-controlled Cas9 repressible system. Mol. Ther. Nucleic Acids 19, 922–932 (2020).
Roy, M. J. et al. SPR-measured dissociation kinetics of PROTAC ternary complexes influence target degradation rate. ACS Chem. Biol. 14, 361–368 (2019).
Robers, M. B. et al. Quantitative, real-time measurements of intracellular target engagement using energy transfer. Methods Mol. Biol. 1888, 45–71 (2019).
Hjerpe, R. et al. Efficient protection and isolation of ubiquitylated proteins using tandem ubiquitin-binding entities. EMBO Rep. 10, 1250–1258 (2009).
Emanuele, M. J. et al. Global identification of modular cullin-RING ligase substrates. Cell 147, 459–474 (2011).
Feng, S. et al. Improved split fluorescent proteins for endogenous protein labeling. Nat. Commun. 8, 370 (2017).
Soucy, T. A. et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 458, 732–736 (2009).
Schlierf, A. et al. Targeted inhibition of the COP9 signalosome for treatment of cancer. Nat. Commun. 7, 13166 (2016).
Anderson, D. J. et al. Targeting the AAA ATPase p97 as an approach to treat cancer through disruption of protein homeostasis. Cancer Cell 28, 653–665 (2015).
Hyer, M. L. et al. A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment. Nat. Med. 24, 186–193 (2018).
Goodsell, D. S., Autin, L. & Olson, A. J. Illustrate: software for biomolecular illustration. Structure 27, 1716–1720.e1 (2019).
We thank all members of the Fischer lab for discussions and insights. This work was supported by NIH grants NCI R01CA214608 and R01CA218278 (to E.S.F.) and a Mark Foundation Emerging Leader Award (to E.S.F.). E.S.F. is a Damon Runyon-Rachleff Innovator supported in part by the Damon Runyon Cancer Research Foundation (DRR-50–18). H.Y. is supported by a Chleck Foundation fellowship.
E.S.F. is a founder, scientific advisory board (SAB) member and equity holder of Civetta Therapeutics. E.S.F. is a SAB member and equity holder of C4 Therapeutics. E.S.F. is or has consulted for Novartis, AbbVie, Astellas, Deerfield, EcoR1 and Pfizer. The Fischer lab receives or has received research funding from Novartis, Deerfield and Astellas.
Editor recognition statement Katarzyna Marcinkiewicz and Anke Sparmann were the primary editors on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Wu, T., Yoon, H., Xiong, Y. et al. Targeted protein degradation as a powerful research tool in basic biology and drug target discovery. Nat Struct Mol Biol (2020). https://doi.org/10.1038/s41594-020-0438-0