Balch, W. E., Morimoto, R. I., Dillin, A. & Kelly, J. W. Adapting proteostasis for disease intervention. Science 319, 916–919 (2008).

Article  CAS  PubMed  Google Scholar 

Li, K. & Crews, C. M. PROTACs: past, present and future. Chem. Soc. Rev. 51, 5214–5236 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Spradlin, J. N., Zhang, E. & Nomura, D. K. Reimagining druggability using chemoproteomic platforms. Acc. Chem. Res. 54, 1801–1813 (2021).

Article  CAS  PubMed  Google Scholar 

Békés, M., Langley, D. R. & Crews, C. M. PROTAC targeted protein degraders: the past is prologue. Nat. Rev. Drug Discov. 21, 181–200 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Liu, X. & Ciulli, A. Proximity-based modalities for biology and medicine. ACS Cent. Sci. 9, 1269–1284 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

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).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chirnomas, D., Hornberger, K. R. & Crews, C. M. Protein degraders enter the clinic—a new approach to cancer therapy. Nat. Rev. Clin. Oncol. 20, 265–278 (2023).

Article  CAS  PubMed  Google Scholar 

Schneider, M. et al. The PROTACtable genome. Nat. Rev. Drug Discov. 20, 789–797 (2021).

Article  CAS  PubMed  Google Scholar 

Weng, G. et al. PROTAC-DB 2.0: an updated database of PROTACs. Nucleic Acids Res. 51, D1367–D1372 (2023).

Article  PubMed  Google Scholar 

Bashore, C. et al. Targeted degradation via direct 26S proteasome recruitment. Nat. Chem. Biol. 19, 55–63 (2023).

Article  CAS  PubMed  Google Scholar 

Ali, E. M. H., Loy, C. A. & Trader, D. J. ByeTAC: bypassing an E3 ligase for targeted protein degradation. Preprint at bioRxiv https://doi.org/10.1101/2024.01.20.576376 (2024).

Takahashi, D. et al. AUTACs: cargo-specific degraders using selective autophagy. Mol. Cell 76, 797–810 (2019).

Article  CAS  PubMed  Google Scholar 

Ji, C. H. et al. The AUTOTAC chemical biology platform for targeted protein degradation via the autophagy-lysosome system. Nat. Commun. 13, 904 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fu, Y. et al. Degradation of lipid droplets by chimeric autophagy-tethering compounds. Cell Res. 31, 965–979 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li, Z. et al. Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds. Nature 575, 203–209 (2019).

Article  CAS  PubMed  Google Scholar 

Ahn, G. et al. LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation. Nat. Chem. Biol. 17, 937–946 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Banik, S. M. et al. Lysosome-targeting chimaeras for degradation of extracellular proteins. Nature 584, 291–297 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ahn, G. et al. Elucidating the cellular determinants of targeted membrane protein degradation by lysosome-targeting chimeras. Science 382, eadf6249 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhou, Y., Teng, P., Montgomery, N. T., Li, X. & Tang, W. Development of triantennary N-acetylgalactosamine conjugates as degraders for extracellular proteins. ACS Cent. Sci. 7, 499–506 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Caianiello, D. F. et al. Bifunctional small molecules that mediate the degradation of extracellular proteins. Nat. Chem. Biol. 17, 947–953 (2021).

Article  CAS  PubMed  Google Scholar 

Wong, E. & Cuervo, A. M. Integration of clearance mechanisms: the proteasome and autophagy. Cold Spring Harb. Perspect. Biol. 2, a006734 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Varshavsky, A. N-degron and C-degron pathways of protein degradation. Proc. Natl Acad. Sci. USA 116, 358–366 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Poirson, J. et al. Proteome-scale discovery of protein degradation and stabilization effectors. Nature 628, 878–886 (2024).

Article  CAS  PubMed  Google Scholar 

Owens, D. D. G. et al. A chemical probe to modulate human GID4 pro/N-degron interactions. Nat. Chem. Biol. 20, 1164–1175 (2024).

Article  CAS  PubMed  Google Scholar 

Ichikawa, S. et al. The E3 ligase adapter cereblon targets the C-terminal cyclic imide degron. Nature 610, 775–782 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Makaros, Y. et al. Ubiquitin-independent proteasomal degradation driven by C-degron pathways. Mol. Cell 83, 1921–1935 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lucas, X. & Ciulli, A. Recognition of substrate degrons by E3 ubiquitin ligases and modulation by small-molecule mimicry strategies. Curr. Opin. Struct. Biol. 44, 101–110 (2017).

Article  CAS  PubMed  Google Scholar 

Nabet, B. et al. The dTAG system for immediate and target-specific protein degradation. Nat. Chem. Biol. 14, 431–441 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Albrecht, L. V., Ploper, D., Tejeda-Muñoz, N. & De Robertis, E. M. Arginine methylation is required for canonical Wnt signaling and endolysosomal trafficking. Proc. Natl Acad. Sci. USA 115, E5317–E5325 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Franco, C. N. et al. Vitamin B6 is governed by the local compartmentalization of metabolic enzymes during growth. Sci. Adv. 9, eadi2232 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Larsen, S. C. et al. Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells. Sci. Signal. 9, rs9 (2016).

Article  PubMed