Breaking BAG: The Co-Chaperone BAG3 in Health and Disease

Trends in Pharmacological Sciences

Volumn 37, Issue 8, 2016, Pages 672-688

  Behl, Christian ^a  

^a UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

Author keywords

BAG1 BAG3 switch; Bcl 2; Hsc Hsp70; macroautophagy; proteasome; protein quality control

Indexed keywords

BAG 1 PROTEIN; BAG 2 PROTEIN; BAG 3 PROTEIN; BAG 3 PROTEIN ANTIBODY; BAG 4 PROTEIN; BAG 5 PROTEIN; BAG 6 PROTEIN; CANTHARIDIN; CHAPERONE; FISETIN; HEAT SHOCK PROTEIN 70; PROTEIN ANTIBODY; PROTEIN BCL 2; PYRROLIDINE DITHIOCARBAMATE; UNCLASSIFIED DRUG; APOPTOSIS REGULATORY PROTEIN; BAG3 PROTEIN, HUMAN; SIGNAL TRANSDUCING ADAPTOR PROTEIN;

AMYOTROPHIC LATERAL SCLEROSIS; AUTOPHAGY; BAG3 GENE; CANCER INHIBITION; CARCINOGENESIS; CELL AGING; DEPRESSION; DRUG EFFECT; DRUG TARGETING; GENE EXPRESSION; GENE MUTATION; GENETIC ASSOCIATION; HUMAN; HUNTINGTON CHOREA; LIVER CELL CARCINOMA; MACROAUTOPHAGY; METASTASIS; MUSCULAR DYSTROPHY; MYOPATHY; NEOPLASM; NERVE DEGENERATION; NONHUMAN; PANCREAS ADENOCARCINOMA; PARKINSON DISEASE; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; ANIMAL; DEGENERATIVE DISEASE; METABOLISM; MUSCLE DISEASE; PATHOLOGY; PHYSIOLOGY;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; APOPTOSIS REGULATORY PROTEINS; AUTOPHAGY; HSP70 HEAT-SHOCK PROTEINS; HUMANS; MUSCULAR DISEASES; NEOPLASMS; NEURODEGENERATIVE DISEASES;

EID: 84965077472     PISSN: 01656147     EISSN: 18733735     Source Type: Journal    
DOI: 10.1016/j.tips.2016.04.007     Document Type: Review

References (158)

1. 1 Hockenbery, D., et al. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348 (1990), 334–336.
2. 2 Hockenbery, D.M., The bcl-2 oncogene and apoptosis. Semin. Immunol. 4 (1992), 413–420.
3. 3 Reed, J.C., Bcl-2 and the regulation of programmed cell death. J. Cell Biol. 124 (1994), 1–6.
4. 4 Chao, D.T., Korsmeyer, S.J., BCL-2 family: regulators of cell death. Annu. Rev. Immunol. 16 (1998), 395–419.
5. 5 Takayama, S., et al. Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity. Cell 80 (1995), 279–284.
6. 6 Takayama, S., et al. An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators. J. Biol. Chem. 274 (1999), 781–786.
7. 7 Doong, H., et al. What's in the ‘BAG’? – A functional domain analysis of the BAG-family proteins. Cancer Lett. 188 (2002), 25–32.
8. 8 Rosati, A., et al. Apoptosis inhibition in cancer cells: a novel molecular pathway that involves BAG3 protein. Int. J. Biochem. Cell Biol. 39 (2007), 1337–1342.
9. 9 Takayama, S., Reed, J.C., Molecular chaperone targeting and regulation by BAG family proteins. Nat. Cell Biol. 3 (2001), E237–E241.
10. 10 Kabbage, M., Dickman, M.B., The BAG proteins: a ubiquitous family of chaperone regulators. Cell Mol. Life Sci. 65 (2008), 1390–1402.
11. 11 Rosati, A., et al. BAG3: a multifaceted protein that regulates major cell pathways. Cell Death Dis., 2, 2011, e141.
12. 12 Sondermann, H., et al. Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70 nucleotide exchange factors. Science 291 (2001), 1553–1557.
13. 13 Sondermann, H., et al. Prediction of novel Bag-1 homologs based on structure/function analysis identifies Snl1p as an Hsp70 co-chaperone in Saccharomyces cerevisiae. J. Biol. Chem. 277 (2002), 33220–33227.
14. 14 Colvin, T.A., et al. Hsp70–Bag3 interactions regulate cancer-related signaling networks. Cancer Res. 74 (2014), 4731–4740.
15. 15 Salah, Z., et al. WW domain-containing proteins: retrospectives and the future. Front. Biosci. 17 (2012), 331–348.
16. 16 Carra, S., et al. HspB8 chaperone activity toward poly(Q)-containing proteins depends on its association with Bag3, a stimulator of macroautophagy. J. Biol. Chem. 283 (2008), 1437–1444.
17. 17 Crippa, V., et al. The small heat shock protein B8 (HspB8) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS). Hum. Mol. Genet. 19 (2010), 3440–3456.
18. 18 Gamerdinger, M., et al. Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3. EMBO J. 28 (2009), 889–901.
19. 19 Gamerdinger, M., et al. BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins. EMBO Rep. 12 (2011), 149–156.
20. 20 Arndt, V., et al. Chaperone-assisted selective autophagy is essential for muscle maintenance. Curr. Biol. 20 (2010), 143–148.
21. 21 Ulbricht, A., et al. Cellular mechanotransduction relies on tension-induced and chaperone-assisted autophagy. Curr. Biol. 23 (2013), 430–435.
22. 22 Ulbricht, A., et al. Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle. Autophagy 11 (2015), 538–546.
23. 23 Höhfeld, J., Jentsch, S., GrpE-like regulation of the hsc70 chaperone by the anti-apoptotic protein BAG-1. EMBO J. 16 (1997), 6209–6216.
24. 24 Bukau, B., et al. Molecular chaperones and protein quality control. Cell 125 (2006), 443–451.
25. 25 Bimston, D., et al. BAG-1, a negative regulator of Hsp70 chaperone activity, uncouples nucleotide hydrolysis from substrate release. EMBO J. 17 (1998), 6871–6878.
26. 26 Lüders, J., et al. The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome. J. Biol. Chem. 275 (2000), 4613–4617.
27. 27 Maeng, S., et al. BAG1 plays a critical role in regulating recovery from both manic-like and depression-like behavioral impairments. Proc. Natl. Acad. Sci. U.S.A. 105 (2008), 8766–8771.
28. 28 Knapp, R.T., et al. Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function. PLoS ONE, 9, 2014, e85415.
29. 29 Götz, R., et al. Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells. Nat. Neurosci. 8 (2005), 1169–1178.
30. 30 Liman, J., et al. Subcellular distribution affects BAG1 function. Brain Res. 1198 (2008), 21–26.
31. 31 Brendel, A., et al. Differential regulation of apoptosis-associated genes by estrogen receptor alpha in human neuroblastoma cells. Restor. Neurol. Neurosci. 31 (2013), 199–211.
32. 32 Challagundla, M., et al. AAV-mediated expression of BAG1 and ROCK2–shRNA promote neuronal survival and axonal sprouting in a rat model of rubrospinal tract injury. J. Neurochem. 134 (2015), 261–275.
33. 33 Arndt, V., et al. BAG-2 acts as an inhibitor of the chaperone-associated ubiquitin ligase CHIP. Mol. Biol. Cell. 16 (2005), 5891–5900.
34. 34 Dai, Q., et al. Regulation of the cytoplasmic quality control protein degradation pathway by BAG2. J. Biol. Chem. 280 (2005), 38673–38681.
35. 35 Carrettiero, D.C., et al. The cochaperone BAG2 sweeps paired helical filament-insoluble tau from the microtubule. J. Neurosci. 29 (2009), 2151–2161.
36. 36 Che, X., et al. The BAG2 protein stabilises PINK1 by decreasing its ubiquitination. Biochem. Biophys. Res. Commun. 441 (2013), 488–492.
37. + via interaction with DJ-1. J. Mol. Neurosci. 55 (2015), 798–802.
38. 38 Yue, X., et al. BAG2 promotes tumorigenesis through enhancing mutant p53 protein levels and function. eLife, 4, 2015, 08401.
39. 39 Jiang, Y., et al. Prevention of constitutive TNF receptor 1 signaling by silencer of death domains. Science 283 (1999), 543–546.
40. 40 Kalia, S.K., et al. BAG5 inhibits parkin and enhances dopaminergic neuron degeneration. Neuron 44 (2004), 931–945.
41. 41 Wang, X., et al. BAG5 protects against mitochondrial oxidative damage through regulating PINK1 degradation. PLoS ONE, 9, 2014, e86276.
42. 42 Kalia, S.K., et al. Molecular chaperones as rational drug targets for Parkinson's disease therapeutics. CNS Neurol. Disord. Drug Targets 9 (2010), 741–753.
43. 43 Beilina, A., et al. Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. Proc. Natl. Acad. Sci. U.S.A. 111 (2014), 2626–2631.
44. 44 Spies, T., et al. Human major histocompatibility complex contains a minimum of 19 genes between the complement cluster and HLA-B. Proc. Natl. Acad. Sci. U.S.A. 86 (1989), 8955–8958.
45. 45 Thress, K., et al. Scythe: a novel reaper-binding apoptotic regulator. EMBO J. 17 (1998), 6135–6143.
46. 46 Thress, K., et al. Reversible inhibition of Hsp70 chaperone function by Scythe and Reaper. EMBO J. 20 (2001), 1033–1041.
47. 47 Desmots, F., et al. The reaper-binding protein scythe modulates apoptosis and proliferation during mammalian development. Mol. Cell. Biol. 25 (2005), 10329–10337.
48. 48 Desmots, F., et al. Scythe regulates apoptosis-inducing factor stability during endoplasmic reticulum stress-induced apoptosis. J. Biol. Chem. 283 (2008), 3264–3271.
49. 49 Corduan, A., et al. Sequential interplay between BAG6 and HSP70 upon heat shock. Cell. Mol. Life Sci. 66 (2009), 1998–2004.
50. 50 Vanoli, A., et al. Chaperone molecules concentrate together with the ubiquitin-proteasome system inside particulate cytoplasmic structures: possible role in metabolism of misfolded proteins. Histochem. Cell Biol. 144 (2015), 179–184.
51. 51 Stefanovic, S., Hegde, R.S., Identification of a targeting factor for posttranslational membrane protein insertion into the ER. Cell 128 (2007), 1147–1159.
52. 52 Mariappan, M., et al. A ribosome-associating factor chaperones tail-anchored membrane proteins. Nature 466 (2010), 1120–1124.
53. 53 Hessa, T., et al. Protein targeting and degradation are coupled for elimination of mislocalized proteins. Nature 475 (2011), 394–397.
54. 54 Wang, Q., et al. A ubiquitin ligase-associated chaperone holdase maintains polypeptides in soluble states for proteasome degradation. Mol. Cell 42 (2011), 758–770.
55. 55 Mock, J.Y., et al. Bag6 complex contains a minimal tail-anchor-targeting module and a mock BAG domain. Proc. Natl. Acad. Sci. U.S.A. 112 (2015), 106–111.
56. 56 Tanaka, H., et al. A conserved island of BAG6/Scythe is related to ubiquitin domains and participates in short hydrophobicity recognition. FEBS J. 283 (2016), 662–677.
57. 57 Saresella, M., et al. A role for the TIM-3/GAL-9/BAT3 pathway in determining the clinical phenotype of multiple sclerosis. FASEB J. 28 (2014), 5000–5009.
58. 58 Chen, J., et al. BAT3 rs1052486 and rs3117582 polymorphisms are associated with lung cancer risk: a meta-analysis. Tumour Biol. 35 (2014), 9855–9858.
59. 59 Bruno, A.P., et al. Identification of a synaptosome-associated form of BAG3 protein. Cell Cycle 7 (2008), 3104–3105.
60. 60 Liao, Q., et al. The anti-apoptotic protein BAG-3 is overexpressed in pancreatic cancer and induced by heat stress in pancreatic cancer cell lines. FEBS Lett. 503 (2001), 151–157.
61. 61 Gentilella, A., Khalili, K., BAG3 expression in glioblastoma cells promotes accumulation of ubiquitinated clients in an Hsp70-dependent manner. J. Biol. Chem. 286 (2011), 9205–9215.
62. 62 Felzen, V., et al. Estrogen receptor α regulates non-canonical autophagy that provides stress resistance to neuroblastoma and breast cancer cells and involves BAG3 function. Cell Death Dis., 6, 2015, e1812.
63. 63 Sherman, M.Y., Gabai, V.L., Hsp70 in cancer: back to the future. Oncogene 34 (2015), 4153–4161.
64. 64 Yang, L., et al. A tumor suppressor and oncogene: the wt1 story. Leukemia 21 (2007), 868–876.
65. 65 Cesaro, E., et al. Wt1 protein is a transcriptional activator of the antiapoptotic bag3 gene. Leukemia 24 (2010), 1204–1206.
66. 66 Gentilella, A., Khalili, K., Autoregulation of co-chaperone BAG3 gene transcription. J. Cell Biochem. 108 (2009), 1117–1124.
67. 67 Gentilella, A., Khalili, K., BAG3 expression is sustained by FGF2 in neural progenitor cells and impacts cell proliferation. Cell Cycle 9 (2010), 4245–4247.
68. 68 Homma, S., et al. BAG3 deficiency results in fulminant myopathy and early lethality. Am. J. Pathol. 169 (2006), 761–773.
69. 69 Youn, D.Y., et al. Bis deficiency results in early lethality with metabolic deterioration and involution of spleen and thymus. Am. J. Physiol. Endocrinol. Metab. 295 (2008), E1349–E1357.
70. 70 Doong, H., et al. CAIR-1/BAG-3 abrogates heat shock protein-70 chaperone complex-mediated protein degradation: accumulation of poly-ubiquitinated Hsp90 client proteins. J. Biol. Chem. 278 (2003), 28490–28500.
71. 71 Fuchs, M., et al. Identification of the key structural motifs involved in HspB8/HspB6-Bag3 interaction. Biochem. J. 425 (2009), 245–255.
72. 72 Gout, E., et al. BAG3 and adenovirus penton base protein partnership. J. Cell. Biochem. 111 (2010), 699–708.
73. 73 Iwasaki, M., BAG3 directly associates with guanine nucleotide exchange factor of Rap1, PDZGEF2, and regulates cell adhesion. Biochem. Biophys. Res. Commun. 400 (2010), 413–418.
74. 74 Doong, H., et al. CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70. Oncogene 19 (2000), 4385–4395.
75. 75 Hishiya, A., et al. Bag3 and hsc70 interact with actin capping protein capz to maintain myofibrillar integrity under mechanical stress. Circ. Res. 107 (2010), 1220–1231.
76. 76 Chen, Y., et al. Bcl2-associated athanogene 3 interactome analysis reveals a new role in modulating proteasome activity. Mol. Cell. Proteomics 12 (2013), 2804–2819.
77. 77 Jin, Y.H., et al. BAG3 affects the nucleocytoplasmic shuttling of HSF1 upon heat stress. Biochem. Biophys. Res. Commun. 464 (2015), 561–567.
78. 78 Li, N., et al. PKCδ-mediated phosphorylation of BAG3 at Ser187 site induces epithelial–mesenchymal transition and enhances invasiveness in thyroid cancer FRO cells. Oncogene 32 (2013), 4539–4548.
79. 79 Ge, F., et al. Identification of novel 14-3-3ζ interacting proteins by quantitative immunoprecipitation combined with knockdown (QUICK). J. Proteome Res. 9 (2010), 5848–5858.
80. 80 Xu, Z., et al. 14-3-3 protein targets misfolded chaperone-associated proteins to aggresomes. J. Cell Sci. 126 (2013), 4173–4186.
81. 81 Kong, D.H., et al. BAG3 elevation inhibits cell proliferation via direct interaction with G6PD in hepatocellular carcinomas. Oncotarget 7 (2016), 700–711.
82. 82 Rosati, A., et al. BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages. Nat. Commun., 6, 2015, 8695.
83. 83 Chiappetta, G., et al. The anti-apoptotic BAG3 protein is expressed in lung carcinomas and regulates small cell lung carcinoma (SCLC) tumor growth. Oncotarget 5 (2014), 6846–6853.
84. 84 Pasillas, M.P., et al. Proteomic analysis reveals a role for Bcl2-associated athanogene 3 and major vault protein in resistance to apoptosis in senescent cells by regulating ERK1/2 activation. Mol. Cell. Proteomics 14 (2015), 1–14.
85. 85 Mani, J., et al. Knockdown of BAG3 sensitizes bladder cancer cells to treatment with the BH3 mimetic ABT-737. World J. Urol. 34 (2016), 197–205.
86. 86 Rapino, F., et al. NIK is required for NF-κB-mediated induction of BAG3 upon inhibition of constitutive protein degradation pathways. Cell Death Dis., 6, 2015, e1692.
87. 87 Zhu, H., et al. Overexpressed BAG3 is a potential therapeutic target in chronic lymphocytic leukemia. Ann. Hematol. 93 (2014), 425–435.
88. 88 Guerriero, L., et al. BAG3 protein expression in melanoma metastatic lymph nodes correlates with patients’ survival. Cell Death Dis., 5, 2014, e1173.
89. 89 Kim, J.A., et al. The natural compound cantharidin induces cancer cell death through inhibition of heat shock protein 70 (HSP70) and Bcl-2-associated athanogene domain 3 (BAG3) expression by blocking heat shock factor 1 (HSF1) binding to promoters. J. Biol. Chem. 288 (2013), 28713–28726.
90. 90 Song, S., et al. Activation of heat shock factor 1 plays a role in pyrrolidine dithiocarbamate-mediated expression of the co-chaperone BAG3. Int. J. Biochem. Cell Biol. 42 (2010), 1856–1863.
91. 91 Kim, J.A., et al. Fisetin, a dietary flavonoid, induces apoptosis of cancer cells by inhibiting HSF1 activity through blocking its binding to the hsp70 promoter. Carcinogenesis 36 (2015), 696–706.
92. 92 Li, X., et al. Validation of the Hsp70–Bag3 protein–protein interaction as a potential therapeutic target in cancer. Mol. Cancer Ther. 14 (2015), 642–648.
93. 93 Selcen, D., et al. Mutation in bag3 causes severe dominant childhood muscular dystrophy. Ann. Neurol. 65 (2009), 83–89.
94. 94 Odgerel, Z., et al. Inheritance patterns and phenotypic features of myofibrillar myopathy associated with a bag3 mutation. Neuromuscul. Disord. 20 (2010), 438–442.
95. 95 Konersman, C.G., et al. BAG3 myofibrillar myopathy presenting with cardiomyopathy. Neuromuscul. Disord. 25 (2015), 418–422.
96. 96 Knezevic, T., et al. BAG3: a new player in the heart failure paradigm. Heart Fail. Rev. 20 (2015), 423–434.
97. 97 Gandhi, P.U., et al. Analysis of BAG3 plasma concentrations in patients with acutely decompensated heart failure. Clin. Chim. Acta 445 (2015), 73–78.
98. 2+ homeostasis in adult mouse ventricular myocytes. J. Mol. Cell. Cardiol. 92 (2016), 10–20.
99. 99 Ghaoui, R., et al. Mutations in HSPB8 causing a new phenotype of distal myopathy and motor neuropathy. Neurology 86 (2016), 391–398.
100. 100 Iorio, V., et al. BAG3 regulates formation of the SNARE complex and insulin secretion. Cell Death Dis., 6, 2015, e1684.
101. 101 Hartl, F.U., Hayer-Hartl, M., Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295 (2002), 1852–1858.
102. 102 Kampinga, H.H., Craig, E.A., The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat. Rev. Mol. Cell Biol. 11 (2010), 579–592.
103. 103 Saibil, H., Chaperone machines for protein folding, unfolding and disaggregation. Nat. Rev. Mol. Cell Biol. 14 (2013), 630–642.
104. 104 Hipp, M.S., et al. Proteostasis impairment in protein-misfolding and -aggregation diseases. Trends Cell Biol. 24 (2014), 506–514.
105. 105 Breusing, N., Grune, T., Regulation of proteasome-mediated protein degradation during oxidative stress and aging. Biol. Chem. 389 (2008), 203–209.
106. 106 Ding, W.X., Yin, X.M., Sorting, recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome. Autophagy 4 (2008), 141–150.
107. 107 Pankiv, S., et al. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J. Biol. Chem. 282 (2007), 24131–24145.
108. 108 Jin, M., Klionsky, D.J., Regulation of autophagy: modulation of the size and number of autophagosomes. FEBS Lett. 588 (2014), 2457–2463.
109. 109 Parzych, K.R., Klionsky, D.J., An overview of autophagy: morphology, mechanism, and regulation. Antioxid. Redox Signal. 20 (2014), 460–473.
110. 110 Kawabata, T., Yoshimori, T., Beyond starvation: an update on the autophagic machinery and its functions. J. Mol. Cell. Cardiol., 2015 Published online December 10, 2015 http://dx.doi.org/10.1016/j.yjmcc.2015.12.005.
111. 111 Schneider, J.L., Cuervo, A.M., Autophagy and human disease: emerging themes. Curr. Opin. Genet. Dev. 26 (2014), 16–23.
112. 112 Klionsky, D.J., et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12 (2016), 1–222.
113. 113 Feng, Y., et al. The machinery of macroautophagy. Cell Res. 24 (2014), 24–41.
114. 114 Khaminets, A., et al. Ubiquitin-dependent and independent signals in selective autophagy. Trends Cell Biol. 26 (2016), 6–16.
115. 115 Lamb, C.A., et al. The autophagosome: origins unknown, biogenesis complex. Nat. Rev. Mol. Cell Biol. 14 (2013), 759–774.
116. 116 Kern, A., et al. The integration of autophagy and cellular trafficking pathways via RAB GAPs. Autophagy 11 (2015), 2393–2397.
117. 117 Klionsky, D.J., Schulman, B.A., Dynamic regulation of macroautophagy by distinctive ubiquitin-like proteins. Nat. Struct. Mol. Biol. 21 (2014), 336–345.
118. 118 Carlsson, S.R., Simonsen, A., Membrane dynamics in autophagosome biogenesis. J. Cell Sci. 128 (2015), 193–205.
119. 119 Wesselborg, S., Stork, B., Autophagy signal transduction by ATG proteins: from hierarchies to networks. Cell. Mol. Life Sci. 72 (2015), 4721–4757.
120. 120 Kopitz, J., et al. Nonselective autophagy of cytosolic enzymes by isolated rat hepatocytes. J. Cell Biol. 111 (1990), 941–953.
121. 121 Slobodkin, M.R., Elazar, Z., The Atg8 family: multifunctional ubiquitin-like key regulators of autophagy. Essays Biochem. 55 (2013), 51–64.
122. 122 Rogov, V., et al. Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. Mol. Cell 53 (2014), 167–178.
123. 123 Stolz, A., et al. Cargo recognition and trafficking in selective autophagy. Nat. Cell. Biol. 16 (2014), 495–501.
124. 124 Alberti, S., et al. BAG-1 – a nucleotide exchange factor of Hsc70 with multiple cellular functions. Cell Stress Chaperones 8 (2003), 225–231.
125. 125 Behl, C., BAG3 and friends: co-chaperones in selective autophagy during aging and disease. Autophagy 7 (2011), 795–798.
126. 126 Minoia, M., et al. BAG3 induces the sequestration of proteasomal clients into cytoplasmic puncta: implications for a proteasome-to-autophagy switch. Autophagy 10 (2014), 1603–1621.
127. 127 Rusmini, P., et al. Aberrant autophagic response in the muscle of a knock-in mouse model of spinal and bulbar muscular atrophy. Sci. Rep., 5, 2015, 15174.
128. 128 Fuchs, M., et al. A role for the chaperone complex BAG3–HSPB8 in actin dynamics, spindle orientation and proper chromosome segregation during mitosis. PLoS Genet., 11, 2015, e1005582.
129. 129 Sarparanta, J., et al. Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. Nat. Genet. 44 (2012), 450–455.
130. 130 Proikas-Cezanne, T., et al. WIPI-1α (WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy. Oncogene 23 (2004), 9314–9325.
131. 131 Proikas-Cezanne, T., et al. WIPI proteins: essential PtdIns3P effectors at the nascent autophagosome. J. Cell Sci. 128 (2015), 207–217.
132. 132 Rodríguez, A.E., et al. BAG3 regulates total MAP1LC3B protein levels through a translational but not transcriptional mechanism. Autophagy 12 (2015), 287–296.
133. 133 Ruparelia, A.A., et al. Zebrafish models of BAG3 myofibrillar myopathy suggest a toxic gain of function leading to BAG3 insufficiency. Acta Neuropathol. 128 (2014), 821–833.
134. 134 Johnston, J.A., et al. Aggresomes: a cellular response to misfolded proteins. J. Cell Biol. 143 (1998), 1883–1898.
135. 135 Kopito, R.R., Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol. 10 (2000), 524–530.
136. 136 Zhang, X., Qian, S.B., Chaperone-mediated hierarchical control in targeting misfolded proteins to aggresomes. Mol. Biol. Cell 22 (2011), 3277–3288.
137. 137 Jia, B., et al. 14-3-3 and aggresome formation: implications in neurodegenerative diseases. Prion, 8, 2014, 28123.
138. 138 Zhao, J., et al. 14-3-3 proteins as potential therapeutic targets. Semin. Cell Dev. Biol. 22 (2011), 705–712.
139. 139 Aghazadeh, Y., Papadopoulos, V., The role of the 14-3-3 protein family in health, disease, and drug development. Drug Discov. Today 21 (2016), 278–287.
140. 140 Morawe, T., et al. Protein homeostasis, aging and Alzheimer's disease. Mol. Neurobiol. 46 (2012), 41–54.
141. 141 Eisele, Y.S., et al. Targeting protein aggregation for the treatment of degenerative diseases. Nat. Rev. Drug Discov. 14 (2015), 759–780.
142. 142 Ciechanover, A., Kwon, Y.T., Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies. Exp. Mol. Med., 7, 2015, e147.
143. 143 Lei, Z., et al. BAG3 facilitates the clearance of endogenous tau in primary neurons. Neurobiol. Aging 36 (2015), 24124–24128.
144. 144 Merabova, N., et al. WW domain of BAG3 is required for the induction of autophagy in glioma cells. J. Cell. Physiol. 230 (2015), 831–841.
145. 145 Seidel, K., et al. The HSPB8–BAG3 chaperone complex is upregulated in astrocytes in the human brain affected by protein aggregation diseases. Neuropathol. Appl. Neurobiol. 38 (2012), 39–53.
146. 146 Renziehausen, J., et al. The cleavage product of amyloid-β protein precursor sAβPPα modulates BAG3-dependent aggresome formation and enhances cellular proteasomal activity. J. Alzheimers Dis. 44 (2015), 879–896.
147. 147 Ivanov, A.A., et al. Targeting protein–protein interactions as an anticancer strategy. Trends Pharmacol. Sci. 34 (2013), 393–400.
148. 148 Hua, Y., et al. High content screening biosensor assay to identify disruptors of p53–hDM2 protein–protein interactions. Methods Mol. Biol. 1278 (2015), 555–565.
149. 149 Levine, B., Kroemer, G., Autophagy in the pathogenesis of disease. Cell 132 (2008), 27–42.
150. 150 Choi, A.M., et al. Autophagy in human health and disease. N. Engl. J. Med. 368 (2013), 651–662.
151. 151 Kroemer, G., Autophagy: a druggable process that is deregulated in aging and human disease. J. Clin. Invest. 125 (2015), 1–4.
152. 152 Nixon, R.A., The role of autophagy in neurodegenerative disease. Nat. Med. 19 (2013), 983–997.
153. 153 Hochfeld, W.E., et al. Therapeutic induction of autophagy to modulate neurodegenerative disease progression. Acta Pharmacol. Sin. 34 (2013), 600–604.
154. 154 Hara, T., et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441 (2006), 885–889.
155. 155 Butler, D., et al. Potential compensatory responses through autophagic/lysosomal pathways in neurodegenerative diseases. Autophagy 2 (2006), 234–237.
156. 156 Belaid, A., et al. Autophagy: moving benchside promises to patient bedsides. Curr. Cancer Drug Targets 15 (2015), 684–702.
157. 157 Huang, Z., et al. Stress management by autophagy: implications for chemoresistance. Int. J. Cancer 139 (2016), 23–32.
158. 158 de Duve, C., The lysosome. Sci. Am. 208 (1963), 64–72.