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http://dx.doi.org/10.14348/molcells.2017.0226

Emerging Paradigm of Crosstalk between Autophagy and the Ubiquitin-Proteasome System  

Nam, Taewook (Department of Biochemistry, College of Life Science and Biotechnology and Yonsei Laboratory Animal Research Center, Yonsei University)
Han, Jong Hyun (Department of Biochemistry, College of Life Science and Biotechnology and Yonsei Laboratory Animal Research Center, Yonsei University)
Devkota, Sushil (Section of Cell and Developmental Biology, University of California San Diego)
Lee, Han-Woong (Department of Biochemistry, College of Life Science and Biotechnology and Yonsei Laboratory Animal Research Center, Yonsei University)
Publication Information
Molecules and Cells / v.40, no.12, 2017 , pp. 897-905 More about this Journal
Abstract
Cellular protein homeostasis is maintained by two major degradation pathways, namely the ubiquitin-proteasome system (UPS) and autophagy. Until recently, the UPS and autophagy were considered to be largely independent systems targeting proteins for degradation in the proteasome and lysosome, respectively. However, the identification of crucial roles of molecular players such as ubiquitin and p62 in both of these pathways as well as the observation that blocking the UPS affects autophagy flux and vice versa has generated interest in studying crosstalk between these pathways. Here, we critically review the current understanding of how the UPS and autophagy execute coordinated protein degradation at the molecular level, and shed light on our recent findings indicating an important role of an autophagy-associated transmembrane protein EI24 as a bridging molecule between the UPS and autophagy that functions by regulating the degradation of several E3 ligases with Really Interesting New Gene (RING)-domains.
Keywords
autophagy; crosstalk; EI24; RING-domain; ubiquitin proteasome system;
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1 Liu, W.J., Ye, L., Huang, W.F., Guo, L.J., Xu, Z.G., Wu, H.L., Yang, C., and Liu, H.F. (2016). p62 links the autophagy pathway and the ubiqutin-proteasome system upon ubiquitinated protein degradation. Cell Mol. Biol. Lett. 21, 29.   DOI
2 Livneh, I., Cohen-Kaplan, V., Cohen-Rosenzweig, C., Avni, N., and Ciechanover, A. (2016). The life cycle of the 26S proteasome: from birth, through regulation and function, and onto its death. Cell Res. 26, 869-885.   DOI
3 Marshall, R.S., Li, F., Gemperline, D.C., Book, A.J., and Vierstra, R.D. (2015). Autophagic degradation of the 26S proteasome is mediated by the dual ATG8/ubiquitin receptor RPN10 in Arabidopsis. Mol. Cell 58, 1053-1066.   DOI
4 Dikic, I. (2017). Proteasomal and autophagic degradation systems. Annu. Rev. Biochem. 86, 193-224.   DOI
5 Feng, Y., He, D., Yao, Z., and Klionsky, D.J. (2014). The machinery of macroautophagy. Cell Re.s 24, 24-41.   DOI
6 Gomes, L.C., Di Benedetto, G., and Scorrano, L. (2011). During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat. Cell Biol. 13, 589-598.   DOI
7 Groll, M. and Huber, R. (2003). Substrate access and processing by the 20S proteasome core particle. Int. J. Biochem. Cell Biol. 35, 606-616.   DOI
8 Gurusamy, N., Lekli, I., Gherghiceanu, M., Popescu, L.M., and Das, D.K. (2009). BAG-1 induces autophagy for cardiac cell survival. Autophagy 5, 120-121.   DOI
9 Tang, F., Wang, B., Li, N., Wu, Y., Jia, J., Suo, T., Chen, Q., Liu, Y.J., and Tang, J. (2011). RNF185, a novel mitochondrial ubiquitin E3 ligase, regulates autophagy through interaction with BNIP1. PLoS One 6, e24367.   DOI
10 Tai, H.C., and Schuman, E.M. (2008). Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction. Nat. Rev. Neurosci. 9, 826-838.   DOI
11 Thrower, J.S., Hoffman, L., Rechsteiner, M., and Pickart, C.M. (2000). Recognition of the polyubiquitin proteolytic signal. EMBO J. 19, 94-102.   DOI
12 Tooze, S.A., and Dikic, I. (2016). Autophagy captures the nobel prize. Cell 167, 1433-1435.   DOI
13 Wang, C., and Wang, X. (2015). The interplay between autophagy and the ubiquitin-proteasome system in cardiac proteotoxicity. Biochim. Biophys. Acta 1852, 188-194.   DOI
14 Watson, J.D., and Crick, F.H. (2003). Molecular structure of nucleic acids. A structure for deoxyribose nucleic acid. 1953. Rev. Invest. Clin. 55, 108-109.
15 Houck, S.A., Ren, H.Y., Madden, V.J., Bonner, J.N., Conlin, M.P., Janovick, J.A., Conn, P.M., and Cyr, D.M. (2014). Quality control autophagy degrades soluble ERAD-resistant conformers of the misfolded membrane protein GnRHR. Mol. Cell 54, 166-179.   DOI
16 Hershko, A. (2005). The ubiquitin system for protein degradation and some of its roles in the control of the cell-division cycle (Nobel lecture). Angew. Chem. Int. Ed. Engl. 44, 5932-5943.   DOI
17 Hershko, A., Heller, H., Elias, S., and Ciechanover, A. (1983). Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown. J. Biol. Chem. 258, 8206-8214.
18 Hewitt, G., Carroll, B., Sarallah, R., Correia-Melo, C., Ogrodnik, M., Nelson, G., Otten, E.G., Manni, D., Antrobus, R., Morgan, B.A., et al. (2016). SQSTM1/p62 mediates crosstalk between autophagy and the UPS in DNA repair. Autophagy 12, 1917-1930.   DOI
19 Youle, R.J., and Narendra, D.P. (2011). Mechanisms of mitophagy. Nat Rev Mol Cell Biol 12, 9-14.
20 Wei, Y., Pattingre, S., Sinha, S., Bassik, M., and Levine, B. (2008). JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol. Cell 30, 678-688.   DOI
21 Zhao, J., Brault, J.J., Schild, A., Cao, P., Sandri, M., Schiaffino, S., Lecker, S.H., and Goldberg, A.L. (2007). FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab. 6, 472-483.   DOI
22 Zhao, Y.G., Zhao, H., Miao, L., Wang, L., Sun, F., and Zhang, H. (2012). The p53-induced gene Ei24 is an essential component of the basal autophagy pathway. J. Biol. Chem. 287, 42053-42063.   DOI
23 Mizushima, N., and Levine, B. (2010). Autophagy in mammalian development and differentiation. Nat. Cell Biol. 12, 823-830.   DOI
24 Zhao, B., Qiang, L., Joseph, J., Kalyanaraman, B., Viollet, B., and He, Y.Y. (2016). Mitochondrial dysfunction activates the AMPK signaling and autophagy to promote cell survival. Genes Dis. 3, 82-87.   DOI
25 Zhou, J., Zhang, Y., Qi, J., Chi, Y., Fan, B., Yu, J.Q., and Chen, Z. (2014). E3 ubiquitin ligase CHIP and NBR1-mediated selective autophagy protect additively against proteotoxicity in plant stress responses. PLoS Genet. 10, e1004116.   DOI
26 Metzger, M.B., Pruneda, J.N., Klevit, R.E., and Weissman, A.M. (2014). RING-type E3 ligases: master manipulators of E2 ubiquitinconjugating enzymes and ubiquitination. Biochim. Biophys. Acta 1843, 47-60.   DOI
27 Meusser, B., Hirsch, C., Jarosch, E., and Sommer, T. (2005). ERAD: the long road to destruction. Nat. Cell Biol. 7, 766-772.   DOI
28 Mizushima, N. (2007). Autophagy: process and function. Genes Dev. 21, 2861-2873.   DOI
29 Moreau, K., Renna, M., and Rubinsztein, D.C. (2013). Connections between SNAREs and autophagy. Trends Biochem. Sci. 38, 57-63.   DOI
30 Nakatogawa, H. (2013). Two ubiquitin-like conjugation systems that mediate membrane formation during autophagy. Essays Biochem. 55, 39-50.   DOI
31 Nandi, D., Tahiliani, P., Kumar, A., and Chandu, D. (2006). The ubiquitin-proteasome system. .J Biosci. 31, 137-155.   DOI
32 Ohsumi, Y. (2014). Historical landmarks of autophagy research. Cell Res. 24, 9-23.   DOI
33 Pandey, U.B., Nie, Z., Batlevi, Y., McCray, B.A., Ritson, G.P., Nedelsky, N.B., Schwartz, S.L., DiProspero, N.A., Knight, M.A., Schuldiner, O., et al. (2007). HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447, 859-863.
34 Park, C., and Cuervo, A.M. (2013). Selective autophagy: talking with the UPS. Cell Biochem. Biophys. 67, 3-13.   DOI
35 Park, M.C., Jeong, H., Son, S.H., Kim, Y., Han, D., Goughnour, P.C., Kang, T., Kwon, N.H., Moon, H.E., Paek, S.H., et al. (2016). Novel morphologic and genetic analysis of cancer cells in a 3D microenvironment identifies STAT3 as a regulator of tumor permeability barrier function. Cancer Res. 76, 1044-1054.   DOI
36 Budenholzer, L., Cheng, C.L., Li, Y., and Hochstrasser, M. (2017). Proteasome structure and Assembly. J. Mol. Biol. 429, 3500-3524.   DOI
37 Araki, K., and Nagata, K. (2011). Protein folding and quality control in the ER. Cold Spring Harb. Perspect. Biol. 3, a007526.
38 Ardley, H.C., and Robinson, P.A. (2005). E3 ubiquitin ligases. Essays Biochem. 41, 15-30.   DOI
39 B'Chir, W., Maurin, A.C., Carraro, V., Averous, J., Jousse, C., Muranishi, Y., Parry, L., Stepien, G., Fafournoux, P., and Bruhat, A. (2013). The eIF2alpha/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic Acids Res. 41, 7683-7699.   DOI
40 Boucas, J., Fritz, C., Schmitt, A., Riabinska, A., Thelen, L., Peifer, M., Leeser, U., Nuernberg, P., Altmueller, J., Gaestel, M., et al. (2015). Label-free protein-RNA interactome znalysis identifies Khsrp signaling downstream of the p38/Mk2 kinase complex as a critical modulator of cell cycle progression. PLoS One 10, e0125745.   DOI
41 Cha-Molstad, H., Sung, K.S., Hwang, J., Kim, K.A., Yu, J.E., Yoo, Y.D., Jang, J.M., Han, D.H., Molstad, M., Kim, J.G., et al. (2015). Aminoterminal arginylation targets endoplasmic reticulum chaperone BiP for autophagy through p62 binding. Nat. Cell Biol. 17, 917-929.   DOI
42 Cha-Molstad, H., Yu, J.E., Feng, Z., Lee, S.H., Kim, J.G., Yang, P., Han, B., Sung, K.W., Yoo, Y.D., Hwang, J., et al. (2017). p62/SQSTM1/Sequestosome-1 is an N-recognin of the N-end rule pathway which modulates autophagosome biogenesis. Nat. Commun. 8, 102.   DOI
43 Chan, N.C., Salazar, A.M., Pham, A.H., Sweredoski, M.J., Kolawa, N.J., Graham, R.L., Hess, S., and Chan, D.C. (2011). Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum. Mol. Genet. 20, 1726-1737.   DOI
44 Schmidt, M., and Finley, D. (2014). Regulation of proteasome activity in health and disease. Biochim. Biophys. Acta 1843, 13-25.   DOI
45 Ravikumar, B., Sarkar, S., Davies, J.E., Futter, M., Garcia-Arencibia, M., Green-Thompson, Z.W., Jimenez-Sanchez, M., Korolchuk, V.I., Lichtenberg, M., Luo, S., et al. (2010). Regulation of mammalian autophagy in physiology and pathophysiology. Physiol. Rev. 90, 1383-1435.   DOI
46 Ruan, L., Zhou, C., Jin, E., Kucharavy, A., Zhang, Y., Wen, Z., Florens, L., and Li, R. (2017). Cytosolic proteostasis through importing of misfolded proteins into mitochondria. Nature 543, 443-446.   DOI
47 Russell, R.C., Yuan, H.X., and Guan, K.L. (2014). Autophagy regulation by nutrient signaling. Cell Res. 24, 42-57.   DOI
48 Schreiber, A., and Peter, M. (2014). Substrate recognition in selective autophagy and the ubiquitin-proteasome system. Biochim. Biophys. Acta 1843, 163-181.   DOI
49 Shen, Y.F., Tang, Y., Zhang, X.J., Huang, K.X., and Le, W.D. (2013). Adaptive changes in autophagy after UPS impairment in Parkinson's disease. Acta Pharmacol. Sin. 34, 667-673.   DOI
50 Sriram, S.M., Kim, B.Y., and Kwon, Y.T. (2011). The N-end rule pathway: emerging functions and molecular principles of substrate recognition. Nat. Rev. Mol. Cell Biol. 12, 735-747.   DOI
51 Streich, F.C., Jr., and Lima, C.D. (2014). Structural and functional insights to ubiquitin-like protein conjugation. Annu. Rev. Biophys. 43, 357-379.   DOI
52 Klionsky, D.J., Abeliovich, H., Agostinis, P., Agrawal, D.K., Aliev, G., Askew, D.S., Baba, M., Baehrecke, E.H., Bahr, B.A., Ballabio, A., et al. (2008). Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 4, 151-175.   DOI
53 Suzuki, K., and Ohsumi, Y. (2007). Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae. FEBS Lett. 581, 2156-2161.   DOI
54 Pickart, C.M. (2004). Back to the future with ubiquitin. Cell 116, 181-190.   DOI
55 Hwang, D., Stephanopoulos, G., and Chan, C. (2004). Inverse modeling using multi-block PLS to determine the environmental conditions that provide optimal cellular function. Bioinformatics 20, 487-499.   DOI
56 Jiang, T., Harder, B., Rojo de la Vega, M., Wong, P.K., Chapman, E. ,and Zhang, D.D. (2015). p62 links autophagy and Nrf2 signaling. Free Radic. Biol. Med. 88, 199-204.   DOI
57 Kirkin, V., McEwan, D.G., Novak, I., and Dikic, I. (2009). A role for ubiquitin in selective autophagy. Mol. Cell 34, 259-269.   DOI
58 Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., et al. (2005). Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J. Cell Biol. 169, 425-434.   DOI
59 Komatsu, M., Waguri, S., Koike, M., Sou, Y.S., Ueno, T., Hara, T., Mizushima, N., Iwata, J., Ezaki, J., Murata, S., et al. (2007). Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131, 1149-1163.   DOI
60 Korolchuk, V.I., Mansilla, A., Menzies, F.M., and Rubinsztein, D.C. (2009a). Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates. Mol. Cell 33, 517-527.   DOI
61 Collins, G.A., and Goldberg, A.L. (2017). The logic of the 26S proteasome. Cell 169, 792-806.   DOI
62 Chude, C.I., and Amaravadi, R.K. (2017). Targeting autophagy in cancer: update on clinical trials and novel inhibitors. Int. J. Mol. Sci. 18.
63 Ciechanover, A. (2005). Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat. Rev. Mol. Cell Biol. 6, 79-87.   DOI
64 Cohen-Kaplan, V., Livneh, I., Avni, N., Cohen-Rosenzweig, C., and Ciechanover, A. (2016). The ubiquitin-proteasome system and autophagy: coordinated and independent activities. Int. J. Biochem. Cell. Biol. 79, 403-418.   DOI
65 Crick, F. (1970). Central dogma of molecular biology. Nature 227, 561-563.   DOI
66 Crighton, D., Wilkinson, S., O'Prey, J., Syed, N., Smith, P., Harrison, P.R., Gasco, M., Garrone, O., Crook, T., and Ryan, K.M. (2006). DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell 126, 121-134.   DOI
67 de Bie, P., and Ciechanover, A. (2011). Ubiquitination of E3 ligases: self-regulation of the ubiquitin system via proteolytic and nonproteolytic mechanisms. Cell Death Differ. 18, 1393-1402.   DOI
68 Devkota, S., Sung, Y.H., Choi, J.M., Lee, J., Ha, N.Y., Kim, H., Cho, B.C., Song, J., and Lee, H.W. (2012). Ei24-deficiency attenuates protein kinase Calpha signaling and skin carcinogenesis in mice. Int. J. Biochem. Cell Biol. 44, 1887-1896.   DOI
69 Korolchuk, V.I., Menzies, F.M., and Rubinsztein, D.C. (2009b). A novel link between autophagy and the ubiquitin-proteasome system. Autophagy 5, 862-863.   DOI
70 Korolchuk, V.I., Menzies, F.M., and Rubinsztein, D.C. (2010). Mechanisms of cross-talk between the ubiquitin-proteasome and autophagy-lysosome systems. FEBS Lett. 584, 1393-1398.   DOI
71 Devkota, S., Jeong, H., Kim, Y., Ali, M., Roh, J.I., Hwang, D., and Lee, H.W. (2016). Functional characterization of EI24-induced autophagy in the degradation of RING-domain E3 ligases. Autophagy 12, 2038-2053.   DOI
72 Choi, J.M., Devkota, S., Sung, Y.H., and Lee, H.W. (2013). EI24 regulates epithelial-to-mesenchymal transition and tumor progression by suppressing TRAF2-mediated NF-kappaB activity. Oncotarget 4, 2383-2396.
73 Lamb, C.A., Yoshimori, T., and Tooze, S.A. (2013). The autophagosome: origins unknown, biogenesis complex. Nat. Rev. Mol. Cell Biol. 14, 759-774.   DOI
74 Kriegenburg, F., Jakopec, V., Poulsen, E.G., Nielsen, S.V., Roguev, A., Krogan, N., Gordon, C., Fleig, U., and Hartmann-Petersen, R. (2014). A chaperone-assisted degradation pathway targets kinetochore proteins to ensure genome stability. PLoS Genet. 10, e1004140.   DOI
75 Kwon, Y.T., and Ciechanover, A. (2017). The ubiquitin code in the ubiquitin-proteasome system and autophagy. Trends Biochem. Sci. 42, 873-886.   DOI
76 Labbadia, J., and Morimoto, R.I. (2015). The biology of proteostasis in aging and disease. Annu. Rev. Biochem. 84, 435-464.   DOI
77 Lee, J., Giordano, S., and Zhang, J. (2012). Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem. J. 441, 523-540.   DOI
78 Lilienbaum, A. (2013). Relationship between the proteasomal system and autophagy. Int. J. Biochem. Mol. Biol. 4, 1-26.