Identification of a novel compound that simultaneously impairs the ubiquitin-proteasome system and autophagy

References

• Sala AJ, Bott LC, Morimoto RI. Shaping proteostasis at the cellular, tissue, and organismal level. J Cell Biol. 2017 May 1;216(5):1231–1241.
   PubMed Web of Science ®Google Scholar
• Schrader EK, Harstad KG, Matouschek A. Targeting proteins for degradation. Nat Chem Biol. 2009 Nov;5(11):815–822.
   PubMed Web of Science ®Google Scholar
• Verhoef LG, Lindsten K, Masucci MG, et al. Aggregate formation inhibits proteasomal degradation of polyglutamine proteins. Hum Mol Genet. 2002;11(22):2689–2700.
   PubMed Web of Science ®Google Scholar
• Sherman MY, Goldberg AL. Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases. Neuron. 2001;29(1):15–32.
   PubMed Web of Science ®Google Scholar
• Dikic I, Elazar Z. Mechanism and medical implications of mammalian autophagy. Nat Rev Mole Cell Biol. 2018 Jun;19(6):349–364.
   PubMed Web of Science ®Google Scholar
• Schaaf MB, Keulers TG, Vooijs MA, et al. LC3/GABARAP family proteins: autophagy-(un)related functions. FASEB J. 2016 Dec;30(12):3961–3978.
   PubMed Web of Science ®Google Scholar
• Lum JJ, DeBerardinis RJ, Thompson CB. Autophagy in metazoans: cell survival in the land of plenty. Nat Rev Mole Cell Biol. 2005 6;Jun(6):439–448.
   Google Scholar
• Hara T, Nakamura K, Matsui M, et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 2006 Apr 19;441(7095):885–889.
   PubMed Web of Science ®Google Scholar
• Komatsu M, Waguri S, Chiba T, et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature. 2006 Jun 15;441(7095):880–884.
   PubMed Web of Science ®Google Scholar
• Garcia-Mata R, Bebok Z, Sorscher EJ, et al. Characterization and dynamics of aggresome formation by a cytosolic GFP-chimera. J Cell Biol. 1999 Sept 20;146(6):1239–1254.
   PubMed Web of Science ®Google Scholar
• Johnston JA, Ward CL, Kopito RR. Aggresomes: a cellular response to misfolded proteins. J Cell Biol. 1998 Dec 28;143(7):1883–1898.
   PubMed Web of Science ®Google Scholar
• Bucciantini M, Giannoni E, Chiti F, et al. Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature. 2002;416(6880):507–511.
   PubMed Web of Science ®Google Scholar
• Guang MHZ, Kavanagh EL, Dunne LP, et al. Targeting proteotoxic stress in cancer: a review of the role that protein quality control pathways play in oncogenesis. Cancers (Basel). 2019 Jan 9;11(1):66.
   PubMed Web of Science ®Google Scholar
• Adams J. Proteasome inhibitors as new anticancer drugs. Curr Opin Oncol. 2002;14(6):628–634.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Pietrocola F, Bravo-San Pedro JM, et al. Autophagy in malignant transformation and cancer progression. EMBO J. 2015 Apr 1;34(7):856–880.
   PubMed Web of Science ®Google Scholar
• Brancolini C, Iuliano L. Proteotoxic stress and cell death in cancer cells. Cancers (Basel). 2020 Aug 23;12(9):2385.
   Web of Science ®Google Scholar
• Fricker LD. Proteasome inhibitor drugs. Annu Rev Pharmacol Toxicol. 2020 Jan 6;60:457–476.
   PubMed Web of Science ®Google Scholar
• Levy JMM, Towers CG, Thorburn A. Targeting autophagy in cancer. Nat Rev Cancer. 2017 Sep;17(9):528–542.
   PubMed Web of Science ®Google Scholar
• Lamark T, Johansen T. Autophagy: links with the proteasome. Curr Opin Cell Biol. 2010 Apr;22(2):192–198.
   PubMed Web of Science ®Google Scholar
• Wang XJ, Yu J, Wong SH, et al. A novel crosstalk between two major protein degradation systems: regulation of proteasomal activity by autophagy. Autophagy. 2013 Oct;9(10):1500–1508.
   PubMed Web of Science ®Google Scholar
• Albornoz N, Bustamante H, Soza A, et al. Cellular responses to proteasome inhibition: molecular mechanisms and beyond. Int J Mol Sci. 2019 Jul 10;20(14):3379.
   Web of Science ®Google Scholar
• Pandey UB, Nie Z, Batlevi Y, et al. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature. 2007 Jun 14;447(7146):859–863.
   PubMed Web of Science ®Google Scholar
• Liu D, Gao M, Yang Y, et al. Inhibition of autophagy promotes cell apoptosis induced by the proteasome inhibitor MG-132 in human esophageal squamous cell carcinoma EC9706 cells. Oncol Lett. 2015 May;9(5):2278–2282.
   PubMed Web of Science ®Google Scholar
• Menendez-Benito V, Verhoef LG, Masucci MG, et al. Endoplasmic reticulum stress compromises the ubiquitin-proteasome system. Hum Mol Genet. 2005;14(19):2787–2799. Epub 2005 Aug 15.
   PubMed Web of Science ®Google Scholar
• Dantuma NP, Lindsten K, Glas R, et al. Short-lived green fluorescent proteins for quantifying ubiquitin/proteasome-dependent proteolysis in living cells. Nat Biotechnol. 2000;18(5):538–543.
   PubMed Web of Science ®Google Scholar
• Johnson ES, Ma PC, Ota IM, et al. A proteolytic pathway that recognizes ubiquitin as a degradation signal. J Biol Chem. 1995;270(29):17442–17456.
   PubMed Web of Science ®Google Scholar
• Gierisch ME, Giovannucci TA, Dantuma NP. Reporter-based screens for the ubiquitin/proteasome system. Front Chem. 2020;8:64.
   PubMed Web of Science ®Google Scholar
• Lipinski CA, Lombardo F, Dominy BW, et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001 Mar 1;46(1–3):3–26.
   PubMed Web of Science ®Google Scholar
• Baell JB, Holloway GA. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J Med Chem. 2010 Apr 8;53(7):2719–2740.
   PubMed Web of Science ®Google Scholar
• Walters WP, Namchuk M. Designing screens: how to make your hits a hit. Nat Rev Drug Discov. 2003 Apr;2(4):259–266.
   PubMed Web of Science ®Google Scholar
• Fang S, Jensen JP, Ludwig RL, et al. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem. 2000 Mar 24;275(12):8945–8951.
   PubMed Web of Science ®Google Scholar
• Huang LE, Gu J, Schau M, et al. Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):7987–7992.
   PubMed Web of Science ®Google Scholar
• Murakami Y, Matsufuji S, Kameji T, et al. Ornithine decarboxylase is degraded by the 26S proteasome without ubiquitination. Nature. 1992 Dec 10;360(6404):597–599.
   PubMed Web of Science ®Google Scholar
• Bence NF, Sampat RM, Kopito RR. Impairment of the ubiquitin-proteasome system by protein aggregation. Science. 2001;292(5521):1552–1555.
   PubMed Web of Science ®Google Scholar
• Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 2021 Jan;17(1):1–382.
   PubMed Web of Science ®Google Scholar
• Jacquin E, Leclerc-Mercier S, Judon C, et al. Pharmacological modulators of autophagy activate a parallel noncanonical pathway driving unconventional LC3 lipidation. Autophagy. 2017 May 4;13(5):854–867.
   PubMed Web of Science ®Google Scholar
• Liu Y, Luo X, Shan H, et al. Niclosamide Triggers Non-Canonical LC3 Lipidation. Cells. 2019 Mar 15;8(3):248.
   Web of Science ®Google Scholar
• Florey O, Overholtzer M. Autophagy proteins in macroendocytic engulfment. Trends Cell Biol. 2012 Jul;22(7):374–380.
   PubMed Web of Science ®Google Scholar
• Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation. Science. 2000 Dec 1;290(5497):1717–1721.
   PubMed Web of Science ®Google Scholar
• Lystad AH, Carlsson SR, de la Ballina LR, et al. Distinct functions of ATG16L1 isoforms in membrane binding and LC3B lipidation in autophagy-related processes. Nat Cell Biol. 2019 Mar;21(3):372–383.
   PubMed Web of Science ®Google Scholar
• Santiago AM, Goncalves DL, Morano KA. Mechanisms of sensing and response to proteotoxic stress. Exp Cell Res. 2020 Oct 15;395(2):112240.
   PubMed Web of Science ®Google Scholar
• Kopito RR. Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol. 2000 Dec;10(12):524–530.
   PubMed Web of Science ®Google Scholar
• Zaarur N, Meriin AB, Bejarano E, et al. Proteasome failure promotes positioning of lysosomes around the aggresome via local block of microtubule-dependent transport. Mol Cell Biol. 2014 Apr;34(7):1336–1348.
   PubMed Web of Science ®Google Scholar
• Pakos-Zebrucka K, Koryga I, Mnich K, et al. The integrated stress response. EMBO Rep. 2016 Oct;17(10):1374–1395.
   PubMed Web of Science ®Google Scholar
• Schmidt EK, Clavarino G, Ceppi M, et al. SUnSET, a nonradioactive method to monitor protein synthesis. Nat Methods. 2009 Apr;6(4):275–277.
   PubMed Web of Science ®Google Scholar
• Bounedjah O, Desforges B, Wu TD, et al. Free mRNA in excess upon polysome dissociation is a scaffold for protein multimerization to form stress granules. Nucleic Acids Res. 2014 Jul;42(13):8678–8691.
   PubMed Web of Science ®Google Scholar
• Mogk A, Bukau B, Kampinga HH. Cellular handling of protein aggregates by disaggregation machines. Mol Cell. 2018 Jan 18;69(2):214–226.
   PubMed Web of Science ®Google Scholar
• Pincus D. Regulation of Hsf1 and the heat shock response. Adv Exp Med Biol. 2020;1243:41–50.
   PubMed Web of Science ®Google Scholar
• Biamonti G, Vourc’h C. Nuclear stress bodies. Cold Spring Harb Perspect Biol. 2010 Jun;2(6):a000695.
   PubMed Web of Science ®Google Scholar
• Park J, Cho J, Song EJ. Ubiquitin-proteasome system (UPS) as a target for anticancer treatment. Arch Pharm Res. 2020 Nov;43(11):1144–1161.
   PubMed Web of Science ®Google Scholar
• Kisselev AF, Van Der Linden WA, Overkleeft HS. Proteasome inhibitors: an expanding army attacking a unique target. Chem Biol. 2012 Jan 27;19(1):99–115.
   PubMed Web of Science ®Google Scholar
• Chou TF, Brown SJ, Minond D, et al. Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4834–4839.
   PubMed Web of Science ®Google Scholar
• Bodnar NO, Rapoport TA. Molecular mechanism of substrate processing by the Cdc48 ATPase complex. Cell. 2017 May 4;169(4):722–735 e9.
   PubMed Web of Science ®Google Scholar
• Ju JS, Fuentealba RA, Miller SE, et al. Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease. J Cell Biol. 2009 Dec 14;187(6):875–888.
   PubMed Web of Science ®Google Scholar
• Beskow A, Grimberg KB, Bott LC, et al. A conserved unfoldase activity for the p97 AAA-ATPase in proteasomal degradation. J Mol Biol. 2009 Dec 11;394(4):732–746.
   PubMed Web of Science ®Google Scholar
• Anderson DJ, Le Moigne R, Djakovic S, et al. Targeting the AAA ATPase p97 as an approach to treat cancer through disruption of protein homeostasis. Cancer Cell. 2015 Nov 9;28(5):653–665.
   PubMed Web of Science ®Google Scholar
• Salomons FA, Menendez-Benito V, Bottcher C, et al. Selective accumulation of aggregation-prone proteasome substrates in response to proteotoxic stress. Mol Cell Biol. 2009 Apr;29(7):1774–1785.
   PubMed Web of Science ®Google Scholar
• Eng KE, Panas MD, Karlsson Hedestam GB, et al. A novel quantitative flow cytometry-based assay for autophagy. Autophagy. 2010 Jul;6(5):634–641.
   PubMed Web of Science ®Google Scholar
• Holland P, Torgersen ML, Sandvig K, et al. LYST affects lysosome size and quantity, but not trafficking or degradation through autophagy or endocytosis. Traffic. 2014 Dec;15(12):1390–1405.
   PubMed Web of Science ®Google Scholar