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Cited by 98Heat shock proteins researchUbiquitin and proteasome pathwaysCell death mechanisms and regulation

BAG2 structure, function and involvement in disease

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Qin, Lixia, Guo, Jifeng, Zheng, Qian, Zhang, Hainan·2016·Cellular & Molecular Biology Letters
DOI 10.1186/s11658-016-0020-2PMC PMC5415834
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Abstract

Bcl2-associated athanogene 2 (BAG2) shares a similar molecular structure and function with other BAG family members. Functioning as a co-chaperone, it interacts with the ATPase domain of the heat shock protein 70 (dHsp70) through its BAG domain. It also interacts with many other molecules and regulates various cellular functions. An increasing number of studies have indicated that BAG2 is involved in the pathogenesis of various diseases, including cancers and neurodegenerative diseases. This paper is a comprehensive review of the structure, functions, and protein interactions of BAG2. We also discuss its roles in diseases, including cancer, Alzheimer's disease, Parkinson's disease and spinocerebellar ataxia type-3. Further research on BAG2 could lead to an understanding of the pathogenesis of these disorders or even to novel therapeutic approaches.

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  1. [1]Takayama S Sato T Krajewski S Kochel K Irie S Millan JA Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity Cell 1995 80 279 84 10.1016/0092-8674(95)90410-7 7834747 · DOI · Paper page
  2. [2]Lee JH Takahashi T Yasuhara N Inazawa J Kamada S Tsujimoto Y Bis, a Bcl-2-binding protein that synergizes with Bcl-2 in preventing cell death Oncogene 1999 18 6183 90 10.1038/sj.onc.1203043 10597216 · DOI
  3. [3]Brive L Takayama S Briknarová K Homma S Ishida SK Reed JC The carboxyl-terminal lobe of Hsc70 ATPase domain is sufficient for binding to BAG1 Biochem Biophys Res Commun 2001 289 1099 105 10.1006/bbrc.2001.6087 11741305 · DOI
  4. [4]Kabbage M Dickman MB The BAG proteins: a ubiquitous family of chaperone regulators Cell Mol Life Sci 2008 65 1390 402 10.1007/s00018-008-7535-2 18264803 PMC11131705 · DOI
  5. [5]Takayama S Xie Z Reed JC An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators J Biol Chem 1999 274 781 6 10.1074/jbc.274.2.781 9873016 · DOI
  6. [6]Takayama S Reed JC Molecular chaperone targeting and regulation by BAG family proteins Nat Cell Biol 2001 3 E237 41 10.1038/ncb1001-e237 11584289 · DOI
  7. [7]Doong H Vrailas A Kohn EC What’s in the ‘BAG’? A functional domain analysis of the BAG-family proteins Cancer Lett 2002 188 25 32 10.1016/S0304-3835(02)00456-1 12406544 · DOI
  8. [8]Slater AA Alokail M Gentle D Yao M Kovacs G Maher ER DNA methylation profiling distinguishes histological subtypes of renal cell carcinoma Epigenetics 2013 8 252 67 10.4161/epi.23817 23428843 PMC3669118 · DOI
  9. [9]Klopflesch R Meyer A Lenze D Hummel M Gruber AD Canine cutaneous peripheral nerve sheath tumours versus fibrosarcomas can be differentiated by neuroectodermal marker genes in their transcriptome J Comp Pathol 2013 148 197 205 10.1016/j.jcpa.2012.06.004 22818216 · DOI
  10. [10]Asperger A Renner C Menzel M Gebhardt R Meixensberger J Gaunitz F Identification of factors involved in the anti-tumor activity of carnosine on glioblastomas using a proteomics approach Cancer Invest 2011 29 272 81 10.3109/07357907.2010.550666 21345069 · DOI
  11. [11]Wang HQ Zhang HY Hao FJ Meng X Guan Y Du ZX Induction of BAG2 protein during proteasome inhibitor-induced apoptosis in thyroid carcinoma cells Br J Pharmacol 2008 155 655 60 10.1038/bjp.2008.302 18660828 PMC2584920 · DOI
  12. [12]Li S Banck M Mujtaba S Zhou MM Sugrue MM Walsh MJ p53-induced growth arrest is regulated by the mitochondrial SirT3 deacetylase PLoS One 2010 5 10.1371/journal.pone.0010486 20463968 PMC2864751 · DOI
  13. [13]Saxena A Banasavadi-Siddegowda YK Fan Y Bhattacharya S Roy G Giovannucci DR Frizzell RA Human heat shock protein 105/110 kDa (Hsp105/110) regulates biogenesis and quality control of misfolded cystic fibrosis transmembrane conductance regulator at multiple levels J Biol Chem 2012 287 19158 70 10.1074/jbc.M111.297580 22505710 PMC3365948 · DOI
  14. [14]Xu Z Page RC Gomes MM Kohli E Nix JC Herr AB Structural basis of nucleotide exchange and client binding by the Hsp70 cochaperone Bag2 Nat Struct Mol Biol 2008 15 1309 17 10.1038/nsmb.1518 19029896 PMC2680549 · DOI
  15. [15]de Paula CA Santiago FE de Oliveira AS Oliveira FA Almeida MC Carrettiero DC The co-chaperone BAG2 mediates cold-induced accumulation of phosphorylated tau in SH-SY5Y Cells Cell Mol Neurobiol 2015 36 593 602 10.1007/s10571-015-0239-x 26208804 PMC11482429 · DOI
  16. [16]Sondermann H Scheufler C Schneider C Hohfeld J Hartl FU Moarefi I Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70 nucleotide exchange factors Science 2001 291 1553 7 10.1126/science.1057268 11222862 · DOI
  17. [17]Page RC Xu Z Amick J Nix JC Misra S Crystallization and preliminary X-ray crystallographic analysis of the Bag2 amino-terminal domain from Mus musculus Acta Crystallogr Sect F: Struct Biol Cryst Commun 2012 68 647 51 10.1107/S1744309112013267 PMC3370901 22684061 · DOI
  18. [18]Takayama S Bimston DN Matsuzawa S Freeman BC Aime-Sempe C Xie Z BAG-1 modulates the chaperone activity of Hsp70Hsc70 EMBO J 1997 16 4887 96 10.1093/emboj/16.16.4887 9305631 PMC1170124 · DOI
  19. [19]Arndt V Daniel C Nastainczyk W Alberti S Höhfeld J BAG-2 acts as an inhibitor of the chaperone-associated ubiquitin ligase CHIP Mol Biol Cell 2005 16 5891 900 10.1091/mbc.E05-07-0660 16207813 PMC1289430 · DOI
  20. [20]Dai Q Qian SB Li HH McDonough H Borchers C Huang D Regulation of the cytoplasmic quality control protein degradation pathway by BAG2 J Bio Chemi 2005 280 38673 81 10.1074/jbc.M507986200 16169850 · DOI
  21. [21]Albanèse V Yam AY Baughman J Parnot C Frydman J Systems analyses reveal two chaperone networks with distinct functions in eukaryotic cells Cell 2006 124 75 88 10.1016/j.cell.2005.11.039 16413483 · DOI
  22. [22]Haslbeck M Franzmann T Weinfurtner D Buchner J Some like it hot: the structure and function of small heat-shock proteins Nat Struct Mol Biol 2005 12 842 6 10.1038/nsmb993 16205709 · DOI
  23. [23]Chen B Retzlaff M Roos T Frydman J Cellular strategies of protein quality control Cold Spring Harb Perspect Biol 2011 3 a004374 10.1101/cshperspect.a004374 21746797 PMC3140689 · DOI
  24. [24]Jiang J Ballinger CA Wu Y Dai Q Cyr DM Höhfeld J CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation J Biol Chem 2001 276 42938 44 10.1074/jbc.M101968200 11557750 · DOI
  25. [25]Ballinger CA Connell P Wu Y Hu Z Thompson LJ Yin LY Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions Mol Cell Biol 1999 19 4535 45 10.1128/MCB.19.6.4535 10330192 PMC104411 · DOI
  26. [26]Connell P Ballinger CA Jiang J Wu Y Thompson LJ Höhfeld J The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins Nat Cell Biol 2001 3 93 6 10.1038/35070170 11146632 · DOI
  27. [27]Ueda K Kosako H Fukui Y Hattori S Proteomic identification of Bcl2-associated athanogene 2 as a novel MAPK-activated protein kinase 2 substrate J Biol Chem 2004 279 41815 21 10.1074/jbc.M406049200 15271996 · DOI
  28. [28]Gano JJ Simon JA A proteomic investigation of ligand-dependent HSP90 complexes reveals CHORDC1 as a novel ADP-dependent HSP90-interacting protein Mol Cell Proteomics 2010 9 255 70 10.1074/mcp.M900261-MCP200 19875381 PMC2830838 · DOI
  29. [29]Sétáló G Jr Singh M Guan X Toran-Allerand CD Estradiol-induced phosphorylation of ERK1/2 in explants of the mouse cerebral cortex: the roles of heatshock protein 90 (Hsp90) and MEK2 J Neurobiol 2002 50 1 12 10.1002/neu.10000 11748628 · DOI
  30. [30]de Oliveira AS Santiago FE Balioni LF Ferrari Mde F Almeida M Carrettiero DC BAG2 expression dictates a functional intracellular switch between the p38-dependent effects of nicotine on tau phosphorylation levels via the α7 nicotinic receptor Exp Neurol 2016 275 69 77 10.1016/j.expneurol.2015.10.005 26496817 · DOI
  31. [31]Kudoh M Knee DA Takayama S Reed JC Bag1 proteins regulate growth and survival of ZR-75-1 human breast cancer cells Cancer Res 2002 6 1904 9 11912172
  32. [32]Romano MF Festa M Pagliuca G Lerose R Bisogni R Chiurazzi F BAG3 protein controls B-chronic lymphocytic leukaemia cell apoptosis Cell Death Differ 2003 10 383 5 10.1038/sj.cdd.4401167 12700638 · DOI
  33. [33]Bruchmann A Roller C Walther TV Schäfer G Lehmusvaara S Visakorpi T Bcl-2 associated athanogene 5 (Bag5) is overexpressed in prostate cancer and inhibits ER-stress induced apoptosis BMC Cancer 2013 13 96 10.1186/1471-2407-13-96 23448667 PMC3598994 · DOI
  34. [34]Tschopp J Martinon F Hofmann K Apoptosis: Silencing the death receptors Curr Biol 1999 9 R381 4 10.1016/S0960-9822(99)80233-4 10339421 · DOI
  35. [35]Binici J Koch J BAG-6, a jack of all trades in health and disease Cell Mol Life Sci 2014 71 1829 37 10.1007/s00018-013-1522-y 24305946 PMC11114047 · DOI
  36. [36]Fontaine SN Sabbagh JJ Baker J Martinez-Licha CR Darling A Dickey CA Cellular factors modulating the mechanism of tau protein aggregation Cell Mol Life Sci 2015 72 1863 679 10.1007/s00018-015-1839-9 25666877 PMC4406819 · DOI
  37. [37]Carrettiero DC Hernandez I Neveu P Papagiannakopoulos T Kosik KS The cochaperone BAG2 sweeps paired helical filament- insoluble tau from the microtubule J Neurosci 2009 29 2151 61 10.1523/JNEUROSCI.4660-08.2009 19228967 PMC2768429 · DOI
  38. [38]Carrettiero DC Santiago FE Motzko-Soares ACP Almeida MC Temperature and toxic Tau in Alzheimer’s disease: new insights Temperature 2016 2 491 8 10.1080/23328940.2015.1096438 PMC4843920 27227069 · DOI
  39. [39]Lukiw WJ Micro-RNA speciation in fetal, adult and Alzheimer’s disease hippocampus Neuroreport 2007 18 297 300 10.1097/WNR.0b013e3280148e8b 17314675 · DOI
  40. [40]Krek A Grün D Poy MN Wolf R Rosenberg L Epstein EJ Combinatorial microRNA target predictions Nat Genet 2005 37 495 500 10.1038/ng1536 15806104 · DOI · Paper page
  41. [41]Grimson A Farh KK Johnston WK Garrett-Engele P Lim LP Bartel DP MicroRNA targeting specificity in mammals: determinants beyond seed pairing Mol Cell 2007 27 91 105 10.1016/j.molcel.2007.06.017 17612493 PMC3800283 · DOI · Paper page
  42. [42]Dickey CA Yue M Lin WL Dickson DW Dunmore JH Lee WC Deletion of the ubiquitin ligase CHIP leads to the accumulation, but not the aggregation, of both endogenous phospho- and caspase-3-cleaved tau species J Neurosci 2006 26 6985 96 10.1523/JNEUROSCI.0746-06.2006 16807328 PMC6673930 · DOI · Paper page
  43. [43]Kim J Lee HJ Lee KW Naturally occurring phytochemicals for the prevention of Alzheimer’s disease J Neurochem 2010 112 1415 30 10.1111/j.1471-4159.2009.06562.x 20050972 · DOI
  44. [44]Patil SP Tran N Geekiyanage H Liu L Chan C Curcumin-induced upregulation of the anti-tau cochaperone BAG2 in primary rat cortical neurons Neurosci Lett 2013 554 121 5 10.1016/j.neulet.2013.09.008 24035895 PMC3825752 · DOI
  45. [45]Santiago FE Almeida MC Carrettiero DC BAG2 is repressed by NF-kB signaling, and its overexpression is sufficient to shift Aβ1-42 from neurotrophic to neurotoxic in undifferentiated SH-SY5Y neuroblastoma J Mol Neurosci 2015 57 83 9 10.1007/s12031-015-0579-5 25985852 · DOI
  46. [46]Zhang J Lou X Yang S He S Yang L Liu M BAG2 is a target of the c-Myc gene and is involved in cellular senescence via the p21(CIP1) pathway Cancer Lett 2012 318 34 41 10.1016/j.canlet.2011.11.033 22146591 · DOI
  47. [47]Halliday GM McCann H The progression of pathology in Parkinson’s disease Ann N Y Acad Sci 2010 1184 188 95 10.1111/j.1749-6632.2009.05118.x 20146698 · DOI
  48. [48]Halliday G Hely M Reid W Morris J The progression of pathology in longitudinally followed patients with Parkinson’s disease Acta Neuropathol 2008 115 409 15 10.1007/s00401-008-0344-8 18231798 · DOI
  49. [49]Bonifati V Rohé CF Breedveld GJ Fabrizio E De Mari M Tassorelli C Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes Neurology 2005 65 87 95 10.1212/01.wnl.0000167546.39375.82 16009891 · DOI
  50. [50]Park J Lee SB Lee S Kim Y Song S Kim S Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin Nature 2006 441 1157 61 10.1038/nature04788 16672980 · DOI · Paper page
  51. [51]Tang B Xiong H Sun P Zhang Y Wang D Hu Z Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson’s disease Hum Mol Genet 2006 15 1816 25 10.1093/hmg/ddl104 16632486 · DOI
  52. [52]Weihofen A Ostaszewski B Minami Y Selkoe DJ Pink1 Parkinson mutations, the Cdc37/Hsp90 chaperones and Parkin all influence the maturation or subcellular distribution of Pink1 Hum Mol Genet 2008 17 602 16 10.1093/hmg/ddm334 18003639 · DOI
  53. [53]Plun-Favreau H Klupsch K Moisoi N Gandhi S Kjaer S Frith D The mitochondrial protease HtrA2 is regulated by Parkinson’s disease-associated kinase PINK1 Nat Cell Biol 2007 9 1243 52 10.1038/ncb1644 17906618 · DOI
  54. [55]Wang X Guo J Fei E Mu Y He S Che X BAG5 protects against mitochondrial oxidative damage through regulating PINK1 degradation PLoS One 2014 9 10.1371/journal.pone.0086276 24475098 PMC3901670 · DOI
  55. [56]Che X Tang B Wang X Chen D Yan X Jiang H The BAG2 protein stabilises PINK1 by decreasing its ubiquitination Biochem Biophys Res Commun 2013 441 488 92 10.1016/j.bbrc.2013.10.086 24383081 · DOI
  56. [57]Park J Lee SB Lee S Kim Y Song S Kim S Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin Nature 2006 7097 1157 61 10.1038/nature04788 16672980 · DOI · Paper page
  57. [58]Clark IE Dodson MW Jiang C Cao JH Huh JR Seol JH Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin Nature 2006 7097 1162 6 10.1038/nature04779 16672981 · DOI · Paper page
  58. [59]Qu D Hage A Don-Carolis K Huang E Joselin A Safarpour F BAG2 gene-mediated regulation of PINK1 protein is critical for mitochondrial translocation of PARKIN and neuronal survival J Biol Chem 2015 51 30441 52 PMC4683266 26538564
  59. [60]Kalia SK Lee S Smith PD Liu L Crocker SJ Thorarinsdottir TE BAG5 inhibits parkin and enhances dopaminergic neuron degeneration Neuron 2004 44 931 45 10.1016/j.neuron.2004.11.026 15603737 · DOI
  60. [61]Chung KK Dawson TM Parkin and Hsp70 sacked by BAG5 Neuron 2004 44 899 901 10.1016/j.neuron.2004.12.007 15603730 · DOI
  61. [62]Paulson H Machado-Joseph disease/spinocerebellar ataxia type 3 Handb Clin Neurol 2012 103 437 49 10.1016/B978-0-444-51892-7.00027-9 21827905 PMC3568768 · DOI
  62. [63]Soong B Cheng C Liu R Shan D Machado-Joseph disease: clinical, molecular, and metabolic characterization in Chinese kindreds Ann Neurol 1997 41 446 52 10.1002/ana.410410407 9124801 · DOI
  63. [64]Fan HC Ho LI Chi CS Chen SJ Peng GS Chan TM Polyglutamine (PolyQ) diseases: genetics to treatments Cell Transplant 2014 23 441 58 10.3727/096368914X678454 24816443 · DOI
  64. [65]Che XQ Tang BS Wang HF Yan XX Jiang H Shen L The BAG2 and BAG5 proteins inhibit the ubiquitination of pathogenic ataxin3-80Q Int J Neurosci 2015 125 390 4 10.3109/00207454.2014.940585 25006867 · DOI

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Authors
Qin, L., Guo, J., Zheng, Q., & Zhang, H.
Affiliations
Central South University (CN)
Corresponding author
Zhang, Hainan
ORCID
Venue
Cellular & Molecular Biology Letters
Publisher
Springer Science and Business Media LLC
Published
2016-09-20
Volume
21
Issue
1
Pages
18-18
ISSN
  • 1425-8153 (ISSN-L)
  • 1689-1392
DOI
10.1186/s11658-016-0020-2
PMC
PMC5415834
OpenAlex
W2537070101
Cited by
98
References
1
Citations by year
2026: 9 · 2025: 9 · 2024: 15 · 2023: 12 · 2022: 13 · 2021: 28 · 2020: 8 · 2018: 4
FWCI
0.12
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cellular & Molecular Biology Letters (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • the Major State Basic Research Development Program of China (2011CB510001)
  • the National Natural Science Foundation of China (81200870, 81000542, 8137405, 81430023, 81130021, 81361120404)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
BAG2, BAG domain, co-chaperones, HSP70, protein-protein interaction, cancer, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, spinocerebellar ataxia type 3, pathogenesis
MeSH terms
Animals, Humans, Neoplasms, Protein Conformation, Molecular Chaperones, Neurodegenerative Diseases

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