Lysosome-targeting chimaeras for degradation of extracellular proteins
Open accessAbstract
The majority of therapies that target individual proteins rely on specific activity-modulating interactions with the target protein-for example, enzyme inhibition or ligand blocking. However, several major classes of therapeutically relevant proteins have unknown or inaccessible activity profiles and so cannot be targeted by such strategies. Protein-degradation platforms such as proteolysis-targeting chimaeras (PROTACs)1,2 and others (for example, dTAGs 3, Trim-Away 4, chaperone-mediated autophagy targeting 5 and SNIPERs 6) have been developed for proteins that are typically difficult to target; however, these methods involve the manipulation of intracellular protein degradation machinery and are therefore fundamentally limited to proteins that contain cytosolic domains to which ligands can bind and recruit the requisite cellular components. Extracellular and membrane-associated proteins-the products of 40% of all protein-encoding genes 7-are key agents in cancer, ageing-related diseases and autoimmune disorders 8, and so a general strategy to selectively degrade these proteins has the potential to improve human health. Here we establish the targeted degradation of extracellular and membrane-associated proteins using conjugates that bind both a cell-surface lysosome-shuttling receptor and the extracellular domain of a target protein. These initial lysosome-targeting chimaeras, which we term LYTACs, consist of a small molecule or antibody fused to chemically synthesized glycopeptide ligands that are agonists of the cation-independent mannose-6-phosphate receptor (CI-M6PR). We use LYTACs to develop a CRISPR interference screen that reveals the biochemical pathway for CI-M6PR-mediated cargo internalization in cell lines, and uncover the exocyst complex as a previously unidentified-but essential-component of this pathway. We demonstrate the scope of this platform through the degradation of therapeutically relevant proteins, including apolipoprotein E4, epidermal growth factor receptor, CD71 and programmed death-ligand 1. Our results establish a modular strategy for directing secreted and membrane proteins for lysosomal degradation, with broad implications for biochemical research and for therapeutics.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
LYTACs are chimeric molecules that combine cell surface lysosomal targeting receptors and extracellular or membrane proteins to expand TPD to extracellular targets; Bertozzi's group developed the first LYTAC molecule, Ab-2, by fusing cetuximab with an M6P-modified peptide, and Ab-2 significantly reduced EGFR levels in HeLa cells.
“Consequently, researchers have proposed lysosomal targeting chimera technologies (LYTACs), chimeric molecules that combine cell surface lysosomal targeting receptors and extracellular or membrane proteins, to expand TPD technologies to extracellular targets. Bertozzi’s group at Stanford University developed the first LYTAC molecule, Ab-2, by fusing cetuximab (ctx), a monoclonal antibody targeting”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [544]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Tissue-based map of the human proteome
Uhlén, M., Fagerberg, L., Hallström, B. M., Lindskog, C., Oksvold, P., Mardinoglu, A., Sivertsson, Å., Kampf, C., Sjöstedt, E., Asplund, A., et al. (2015) · Science · doi:10.1126/science.1260419 · Cited by 15,286 · see citing works
The Perseus computational platform for comprehensive analysis of (prote)omics data
Tyanova, S., Temu, T., Sinitcyn, P. G., Carlson, A., Hein, M. Y., Geiger, T., Mann, M., & Cox, J. (2016) · Nature Methods · doi:10.1038/nmeth.3901 · Cited by 7,977 · see citing works
Andromeda: A Peptide Search Engine Integrated into the MaxQuant Environment
Cox, J., Neuhauser, N., Michalski, A., Scheltema, R. A., Olsen, J. V., & Mann, M. (2011) · Journal of Proteome Research · doi:10.1021/pr101065j · Cited by 5,350 · see citing works
Cox, J., Hein, M. Y., Luber, C. A., Paron, I., Nagaraj, N., & Mann, M. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.031591 · Cited by 5,180 · see citing works
The MaxQuant computational platform for mass spectrometry-based shotgun proteomics
Tyanova, S., Temu, T., & Cox, J. (2016) · Nature Protocols · doi:10.1038/nprot.2016.136 · Cited by 4,691 · see citing works
Elias, J. E., & Gygi, S. P. (2007) · Nature Methods · doi:10.1038/nmeth1019 · Cited by 3,925 · see citing works
GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists
Eden, E., Navon, R., Steinfeld, I., Lipson, D., & Yakhini, Z. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-48 · Cited by 3,356 · see citing works
Li, W., Xu, H., Xiao, T., Cong, L., Love, M. I., Zhang, F., Irizarry, R. A., Liu, J. S., Brown, M., & Liu, X. S. (2014) · Genome Biology · doi:10.1186/s13059-014-0554-4 · Cited by 2,684 · see citing works
Sakamoto, K. M., Kim, K. B., Kumagai, A., Mercurio, F., Crews, C. M., & Deshaies, R. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.141230798 · Cited by 2,609 · see citing works
Phthalimide conjugation as a strategy for in vivo target protein degradation
Winter, G. E., Buckley, D. L., Paulk, J., Roberts, J. M., Souza, A., Dhe-Paganon, S., & Bradner, J. E. (2015) · Science · doi:10.1126/science.aab1433 · Cited by 1,760 · see citing works
The dTAG system for immediate and target-specific protein degradation
Nabet, B., Roberts, J. M., Buckley, D. L., Paulk, J., Dastjerdi, S., Yang, A., Leggett, A. L., Erb, M. A., Lawlor, M. A., Souza, A., et al. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0021-8 · Cited by 1,118 · see citing works
Mannose 6-phosphate receptors: new twists in the tale
Ghosh, P., Dahms, N. M., & Kornfeld, S. A. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1050 · Cited by 1,086 · see citing works
CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity
Burr, M. L., Sparbier, C. E., Chan, Y.-C., Williamson, J. C., Woods, K., Beavis, P. A., Lam, E. Y. N., Henderson, M. A., Bell, C. C., Stolzenburg, S., et al. (2017) · Nature · doi:10.1038/nature23643 · Cited by 946 · see citing works
Horlbeck, M. A., Gilbert, L. A., Villalta, J. E., Adamson, B., Pak, R. A., Chen, Y., Fields, A. P., Park, C. Y., Corn, J. E., Kampmann, M., et al. (2016) · eLife · doi:10.7554/elife.19760 · Cited by 894 · see citing works
The position of lysosomes within the cell determines their luminal pH
Johnson, D. E., Ostrowski, P., Jaumouillé, V., & Grinstein, S. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201507112 · Cited by 590 · see citing works
A Method for the Acute and Rapid Degradation of Endogenous Proteins
Clift, D., McEwan, W. A., Labzin, L. I., Konieczny, V., Mogessie, B., James, L. C., & Schuh, M. (2017) · Cell · doi:10.1016/j.cell.2017.10.033 · Cited by 531 · see citing works
Li, J. Y., Perry, S. R., Muniz-Medina, V. M., Wang, X., Wetzel, L. K., Rebelatto, M. C., Hinrichs, M. J., Bezabeh, B. Z., Fleming, R. L., Dimasi, N., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2015.12.008 · Cited by 400 · see citing works
Transferrin receptor 1 in cancer: a new sight for cancer therapy.
Shen, Y., Li, X., Dong, D., Zhang, B., Xue, Y., & Shang, P. (2018) · Europe PMC (PubMed Central) · Cited by 357 · see citing works
Exorcising the Exocyst Complex
Heider, M. R., & Munson, M. (2012) · Traffic · doi:10.1111/j.1600-0854.2012.01353.x · Cited by 344 · see citing works
Zhu, J., Blenis, J., & Yuan, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802785105 · Cited by 246 · see citing works
Rapid and reversible knockdown of endogenous proteins by peptide-directed lysosomal degradation
Fan, X., Wu, J., Lu, J., Wang, J., & Wang, Y. T. (2014) · Nature Neuroscience · doi:10.1038/nn.3637 · Cited by 213 · see citing works
EGFR oligomerization organizes kinase-active dimers into competent signalling platforms
Needham, S. R., Roberts, S. K., Arkhipov, A. S., Mysore, V. P., Tynan, C. J., Zanetti-Domingues, L. C., Kim, E. T., Losasso, V., Korovesis, D., Hirsch, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms13307 · Cited by 203 · see citing works
Molecular basis for multimerization in the activation of the epidermal growth factor receptor
Huang, Y., Bharill, S., Karandur, D., Peterson, S. M., Marita, M., Shi, X., Kaliszewski, M. J., Smith, A. W., Isacoff, E. Y., & Kuriyan, J. (2016) · eLife · doi:10.7554/elife.14107 · Cited by 192 · see citing works
Mannose 6-Phosphate Receptor Targeting and its Applications in Human Diseases
Gary‐Bobo, M., Nirdé, P., Jeanjean, A., Morère, A., & Garcia, M. (2007) · Current Medicinal Chemistry · doi:10.2174/092986707782794005 · Cited by 185 · see citing works
SNIPERs—Hijacking IAP activity to induce protein degradation
Naito, M., Ohoka, N., & Shibata, N. (2019) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2018.12.002 · Cited by 167 · see citing works
Yamazaki, Y., Painter, M. M., Bu, G., & Kanekiyo, T. (2016) · CNS Drugs · doi:10.1007/s40263-016-0361-4 · Cited by 166 · see citing works
Spangler, J. B., Neil, J. R., Abramovitch, S., Yarden, Y., White, F. M., Lauffenburger, D. A., & Wittrup, K. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913476107 · Cited by 149 · see citing works
Beljaars, L., Molema, G., Weert, B., Bonnema, H., Olinga, P., Groothuis, G. M. M., Meijer, D. K. F., & Poelstra, K. (1999) · Hepatology · doi:10.1002/hep.510290526 · Cited by 146 · see citing works
The role of EGF ‐ EGFR signalling pathway in hepatocellular carcinoma inflammatory microenvironment
Huang, P., Xu, X., Wang, L., Zhu, B., Wang, X., & Xia, J. (2013) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12153 · Cited by 123 · see citing works
A shortcut to the lysosome: The mannose-6-phosphate-independent pathway
Coutinho, M. F., Prata, M. J., & Alves, S. (2012) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2012.07.012 · Cited by 121 · see citing works
Chemically tunable mucin chimeras assembled on living cells
Kramer, J. R., Onoa, B., Bustamante, C., & Bertozzi, C. R. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516127112 · Cited by 121 · see citing works
Self-citationIgawa, T., Haraya, K., & Hattori, K. (2016) · Immunological Reviews · doi:10.1111/imr.12392 · Cited by 99 · see citing works
Weissman, A. M., Klausner, R. D., Rao, K., & Harford, J. B. (1986) · The Journal of Cell Biology · doi:10.1083/jcb.102.3.951 · Cited by 96 · see citing works
Zhu, Y., Li, X., Kyazike, J., Zhou, Q., Thurberg, B. L., Raben, N., Mattaliano, R. J., & Cheng, S. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409676200 · Cited by 89 · see citing works
Kampmann, M., Bassik, M. C., & Weissman, J. S. (2014) · Nature Protocols · doi:10.1038/nprot.2014.103 · Cited by 87 · see citing works
Folate receptors targeted to clathrin-coated pits cannot regulate vitamin uptake.
Ritter, T. E., Fajardo, O., Matsue, H., Anderson, R. G. W., & Lacey, S. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.9.3824 · Cited by 83 · see citing works
The human secretome atlas initiative: Implications in health and disease conditions
Brown, K. J., Seol, H., Pillai, D. K., Sankoorikal, B.-J., Formolo, C. A., Mac, J. T., Edwards, N. J., Rose, M. C., & Hathout, Y. (2013) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2013.04.007 · Cited by 72 · see citing works
Improved Precursor Characterization for Data-Dependent Mass Spectrometry
Hebert, A. S., Thöing, C., Riley, N. M., Kwiecien, N. W., Shiskova, E., Huguet, R., Cardasis, H. L., Kuehn, A., Eliuk, S., Zabrouskov, V., et al. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.7b04808 · Cited by 67 · see citing works
Self-citationSly, W. S., Vogler, C. A., Grubb, J. H., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607053103 · Cited by 56 · see citing works
Berkowitz, D. B., Maiti, G., Charette, B. D., et al. (2004) · Organic Letters · doi:10.1021/ol0479444 · Cited by 49 · see citing works
Jeanjean, A., Garcia, M., Leydet, A., et al. (2006) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2006.01.024 · Cited by 44 · see citing works
Liu, L., Lee, W., Doray, B., & Kornfeld, S. A. (2017) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2017.03.006 · Cited by 41 · see citing works
Das, S., Parekh, N. A., Mondal, B., et al. (2016) · ACS Macro Letters · doi:10.1021/acsmacrolett.6b00297 · Cited by 37 · see citing works
Jeanjean, A., Gary‐Bobo, M., Nirdé, P., et al. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.09.101 · Cited by 32 · see citing works
Affinity cleavage of cell surface antibodies using the avidin-biotin system
Alon, R., Bayer, E. A., & Wilchek, M. (1993) · Journal of Immunological Methods · doi:10.1016/0022-1759(93)90114-m · Cited by 6 · see citing works
A Flexible Route to Mannose 6-Phosphonate Functionalized Derivatives
Vidal, S., Montero, J., Leydet, A., et al. (2002) · Phosphorus, sulfur, and silicon and the related elements · doi:10.1080/10426500214297 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
PROTAC targeted protein degraders: the past is prologue
Békés, M., Langley, D. R., & Crews, C. M. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00371-6 · Cited by 3,395 · see citing works
Oughtred, R., Rust, J., Chang, C., Breitkreutz, B., Stark, C., Willems, A., Boucher, L., Leung, G., Kolas, N., Zhang, F., et al. (2021) · Protein Science · doi:10.1002/pro.3978 · Cited by 1,858 · see citing works
Targeting p53 pathways: mechanisms, structures, and advances in therapy
Wang, H., Guo, M., Wei, H., & Chen, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01347-1 · Cited by 1,016 · see citing works
Exploring the next generation of antibody–drug conjugates
Tsuchikama, K., Anami, Y., Ha, S. Y. Y., & Yamazaki, C. M. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00850-2 · Cited by 659 · see citing works
Cotton, A. D., Nguyen, D. P., Gramespacher, J. A., Seiple, I. B., & Wells, J. A. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.0c10008 · Cited by 551 · see citing works
Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works
Tau-targeting therapies for Alzheimer disease: Current status and future directions
Congdon, E. E., Ji, C., Tetlow, A. M., Jiang, Y., & Sigurdsson, E. M. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00883-2 · Cited by 371 · see citing works
Deubiquitinase-targeting chimeras for targeted protein stabilization
Henning, N. J., Boike, L., Spradlin, J. N., Ward, C. C., Liu, G., Zhang, E., Belcher, B. P., Brittain, S. M., Hesse, M. J., Dovala, D., et al. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-00971-2 · Cited by 344 · see citing works
Ji, C. H., Kim, H. Y., Lee, M. J., Heo, A. J., Park, D. Y., Lim, S., Shin, S., Ganipisetti, S., Yang, W. S., Jung, C. A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28520-4 · Cited by 350 · see citing works
The BET family in immunity and disease
Wang, N., Wu, R., Tang, D., & Kang, R. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00384-4 · Cited by 295 · see citing works
Antibody targeting of E3 ubiquitin ligases for receptor degradation
Marei, H., Tsai, W.-T. K., Kee, Y.-S., Ruiz, K., He, J., Cox, C., Sun, T., Penikalapati, S., Dwivedi, P., Choi, M., et al. (2022) · Nature · doi:10.1038/s41586-022-05235-6 · Cited by 273 · see citing works
Pance, K., Gramespacher, J. A., Byrnes, J. R., Salangsang, F., Serrano, J.-A. C., Cotton, A. D., Steri, V., & Wells, J. A. (2023) · Nature Biotechnology · doi:10.1038/s41587-022-01456-2 · Cited by 265 · see citing works
Schneider, M., Radoux, C. J., Hercules, A., Ochoa, D., Dunham, I., Zalmas, L.-P., Hessler, G., Ruf, S., Shanmugasundaram, V., Hann, M. M., et al. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00245-x · Cited by 273 · see citing works
Bifunctional small molecules that mediate the degradation of extracellular proteins
Caianiello, D. F., Zhang, M., Ray, J. D., Howell, R. A., Swartzel, J. C., Branham, E. M. J., Chirkin, E., Sabbasani, V. R., Gong, A. Z., McDonald, D. M., et al. (2021) · Nature Chemical Biology · doi:10.1038/s41589-021-00851-1 · Cited by 244 · see citing works
Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity
Imaide, S., Riching, K. M., Makukhin, N., Vetma, V., Whitworth, C., Hughes, S. J., Trainor, N., Mahan, S. D., Murphy, N., Cowan, A. D., et al. (2021) · Nature Chemical Biology · doi:10.1038/s41589-021-00878-4 · Cited by 251 · see citing works
Chasing 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
Reimagining Druggability Using Chemoproteomic Platforms
Spradlin, J. N., Zhang, E., & Nomura, D. K. (2021) · Accounts of Chemical Research · doi:10.1021/acs.accounts.1c00065 · Cited by 176 · see citing works
Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide
Jan, M., Sperling, A. S., & Ebert, B. L. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00479-z · Cited by 137 · see citing works
Ligandability of E3 Ligases for Targeted Protein Degradation Applications
Belcher, B. P., Ward, C. C., & Nomura, D. K. (2023) · Biochemistry · doi:10.1021/acs.biochem.1c00464 · Cited by 132 · see citing works
Targeting Lysosomal Degradation Pathways: New Strategies and Techniques for Drug Discovery
Pei, J., Wang, G., Feng, L., Zhang, J., Jiang, T., Sun, Q., & Ouyang, L. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01689 · Cited by 124 · see citing works
Progress and Challenges in Targeted Protein Degradation for Neurodegenerative Disease Therapy
Fang, Y., Wang, J., Zhao, M., Zheng, Q., Ren, C., Wang, Y., & Zhang, J. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00844 · Cited by 100 · see citing works
Li, W., Zhang, J., Guo, L., & Wang, Q. (2022) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.1c01150 · Cited by 63 · see citing works
A New Wave of Targeting ‘Undruggable’ Wnt Signaling for Cancer Therapy: Challenges and Opportunities
Park, W.-J., & Kim, M. J. (2023) · Cells · doi:10.3390/cells12081110 · Cited by 57 · see citing works
Advancing Targeted Protein Degradation via Multiomics Profiling and Artificial Intelligence
Duran-Frigola, M., Cigler, M., & Winter, G. E. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.2c11098 · Cited by 50 · see citing works
Application of Novel Degraders Employing Autophagy for Expediting Medicinal Research
Li, X., Liu, Q., Xie, X., Peng, C., Pang, Q., Liu, B., & Han, B. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01712 · Cited by 46 · see citing works
Small-Molecule Degraders beyond PROTACs—Challenges and Opportunities
Kastl, J. M., Davies, G., Godsman, E., & Holdgate, G. A. (2021) · SLAS Discovery · doi:10.1177/2472555221991104 · Cited by 43 · see citing works
Molecular glue degraders: exciting opportunities for novel drug discovery
Lemaitre, T., Cornu, M., Schwalen, F., Since, M., Kieffer, C., & Voisin-Chiret, A. S. (2024) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2024.2306845 · Cited by 36 · see citing works
Unifying Catalysis Framework to Dissect Proteasomal Degradation Paradigms
Rodriguez-Rivera, F. P., & Levi, S. M. (2021) · ACS Central Science · doi:10.1021/acscentsci.1c00389 · Cited by 30 · see citing works
Targeted protein modification as a paradigm shift in drug discovery
Amirian, R., Azadi Badrbani, M., Izadi, Z., Samadian, H., Bahrami, G., Sarvari, S., Abdolmaleki, S., Nabavi, S. M., Derakhshankhah, H., & Jaymand, M. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115765 · Cited by 18 · see citing works
From serendipity to strategy: molecular glue degraders in cancer therapeutics
Darling, S., Bajrami, I., & West, S. C. (2025) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2025.2564068 · Cited by 10 · see citing works
“Other bivalent degraders follow a similar logic: lysosome-targeting chimeras (lytAcs) engage lysosomal degradation pathways (Banik et al. 2020) whereas autophagy-targeting chime-ras (AutAcs) interact with autophagosomal components to initiate autophagy (li et al. 2019; takahashi et al. 2019).”
- Authors
- Banik, S. M., Pedram, K., Wisnovsky, S., Ahn, G., Riley, N. M., & Bertozzi, C. R.
- Affiliations
- Stanford University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Bertozzi, Carolyn R.
- Venue
- Nature
- Published
- 2020-07-29
- Volume
- 584
- Issue
- 7820
- Pages
- 291-297
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7727926
- OpenAlex
- W3045619116
- Cited by
- 1,199
- References
- 46
- Citations by year
- 2026: 259 · 2025: 273 · 2024: 216 · 2023: 182 · 2022: 141 · 2021: 97 · 2020: 27 · 2019: 1 · 2014: 1
- FWCI
- 36.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (K00 CA21245403)
- National Cancer Institute (K00CA212454, P30CA124435, R01CA227942)
- National Institute of General Medical Sciences (T32GM120007)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- lysosome-targeting chimeras, targeted protein degradation, extracellular proteins, membrane proteins, cation-independent mannose 6-phosphate receptor, exocyst complex, CRISPR interference screen, APOE ε4, epidermal growth factor receptor, transferrin receptor, PD-L1, lysosomal degradation
- MeSH terms
- Protein Domains, Animals, Antibodies, Cell Line, Extracellular Space, Female, Glycopeptides, Humans, Ligands, Lysosomes, Membrane Proteins, Receptors, Transferrin, Recombinant Fusion Proteins, Solubility, Substrate Specificity, Antigens, CD, Receptor, IGF Type 2, Protein Transport, Mice, Apolipoprotein E4, Proteolysis, B7-H1 Antigen, CRISPR-Cas Systems, ErbB Receptors
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
