A Role for the Chaperone Complex BAG3-HSPB8 in Actin Dynamics, Spindle Orientation and Proper Chromosome Segregation during Mitosis

1. Saibil H. Chaperone machines for protein folding, unfolding and disaggregation. Nat Rev Mol Cell Biol. 2013;14(10):630–42. Epub 2013/09/13. doi: 10.1038/nrm3658 24026055

2. Quinlan RA, Ellis RJ. Chaperones: needed for both the good times and the bad times. Philosophical transactions of the Royal Society of London Series B, Biological sciences. 2013;368(1617):20130091. Epub 2013/03/27. doi: 10.1098/rstb.2013.0091 23530265

3. Taipale M, Tucker G, Peng J, Krykbaeva I, Lin ZY, Larsen B, et al. A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways. Cell. 2014;158(2):434–48. Epub 2014/07/19. doi: 10.1016/j.cell.2014.05.039 25036637

4. Luo J, Solimini NL, Elledge SJ. Principles of cancer therapy: oncogene and non-oncogene addiction. Cell. 2009;136(5):823–37. doi: 10.1016/j.cell.2009.02.024 19269363

5. Tang Z, Dai S, He Y, Doty RA, Shultz LD, Sampson SB, et al. MEK guards proteome stability and inhibits tumor-suppressive amyloidogenesis via HSF1. Cell. 2015;160(4):729–44. Epub 2015/02/14. doi: 10.1016/j.cell.2015.01.028 25679764

6. Basha E, O'Neill H, Vierling E. Small heat shock proteins and alpha-crystallins: dynamic proteins with flexible functions. Trends Biochem Sci. 2012;37(3):106–17. Epub 2011/12/20. doi: 10.1016/j.tibs.2011.11.005 22177323

7. McHaourab HS, Godar JA, Stewart PL. Structure and mechanism of protein stability sensors: chaperone activity of small heat shock proteins. Biochemistry. 2009;48(18):3828–37. Epub 2009/03/28. doi: 10.1021/bi900212j 19323523

8. Kampinga HH, Garrido C. HSPBs: small proteins with big implications in human disease. The international journal of biochemistry & cell biology. 2012;44(10):1706–10. Epub 2012/06/23.

9. Guilbert Solenn M., Varlet Alice-Anaïs, Fuchs Margit, Lambert Herman, and L J, Lavoie JN. Regulation of Actin-Based Structure Dynamics by HspB Proteins and Partners. In: The Big Book of Small Heat Shock Proteins. Editors Tanguay R.M. and Hightower L.E.. ISBN: 978-3-319-16076-4.: Springer international Publishing AG 2015.

10. Garrido C, Paul C, Seigneuric R, Kampinga HH. The small heat shock proteins family: the long forgotten chaperones. The international journal of biochemistry & cell biology. 2012;44(10):1588–92. Epub 2012/03/28.

11. Carra S, Seguin SJ, Landry J. HspB8 and Bag3: a new chaperone complex targeting misfolded proteins to macroautophagy. Autophagy. 2008;4(2):237–9. Epub 2007/12/21. 18094623

12. Knezevic T, Myers VD, Gordon J, Tilley DG, Sharp TE 3rd, Wang J, et al. BAG3: a new player in the heart failure paradigm. Heart failure reviews. 2015. Epub 2015/05/01.

13. Rosati A, Graziano V, De Laurenzi V, Pascale M, Turco MC. BAG3: a multifaceted protein that regulates major cell pathways. Cell death & disease. 2011;2:e141. Epub 2011/04/08.

14. Kabbage M, Dickman MB. The BAG proteins: a ubiquitous family of chaperone regulators. Cell Mol Life Sci. 2008;65(9):1390–402. Epub 2008/02/12. d doi: 10.1007/s00018-008-7535-2 18264803

15. Carra S, Seguin SJ, Lambert H, Landry J. HspB8 chaperone activity toward poly(Q)-containing proteins depends on its association with Bag3, a stimulator of macroautophagy. J Biol Chem. 2008;283(3):1437–44. Epub 2007/11/17. 18006506

16. Gamerdinger M, Kaya AM, Wolfrum U, Clement AM, Behl C. BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins. EMBO Rep. 2011;12(2):149–56. Epub 2011/01/22. doi: 10.1038/embor.2010.203 21252941

17. Xu Z, Graham K, Foote M, Liang F, Rizkallah R, Hurt M, et al. 14-3-3 protein targets misfolded chaperone-associated proteins to aggresomes. J Cell Sci. 2013;126(Pt 18):4173–86. Epub 2013/07/12. doi: 10.1242/jcs.126102 23843611

18. Minoia M, Boncoraglio A, Vinet J, Morelli FF, Brunsting JF, Poletti A, et al. BAG3 induces the sequestration of proteasomal clients into cytoplasmic puncta: implications for a proteasome-to-autophagy switch. Autophagy. 2014;10(9):1603–21. Epub 2014/07/22. doi: 10.4161/auto.29409 25046115

19. Kopito RR. Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol. 2000;10(12):524–30. Epub 2000/12/21. 11121744

20. Merabova N, Sariyer IK, Saribas AS, Knezevic T, Gordon J, Turco MC, et al. WW domain of BAG3 is required for the induction of autophagy in glioma cells. Journal of cellular physiology. 2015;230(4):831–41. Epub 2014/09/11. doi: 10.1002/jcp.24811 25204229

21. Homma S, Iwasaki M, Shelton GD, Engvall E, Reed JC, Takayama S. BAG3 deficiency results in fulminant myopathy and early lethality. Am J Pathol. 2006;169(3):761–73. Epub 2006/08/29. 16936253

22. Hishiya A, Kitazawa T, Takayama S. BAG3 and Hsc70 interact with actin capping protein CapZ to maintain myofibrillar integrity under mechanical stress. Circulation research. 2010;107(10):1220–31. Epub 2010/10/05. doi: 10.1161/CIRCRESAHA.110.225649 20884878

23. Arndt V, Dick N, Tawo R, Dreiseidler M, Wenzel D, Hesse M, et al. Chaperone-assisted selective autophagy is essential for muscle maintenance. Curr Biol. 2010;20(2):143–8. Epub 2010/01/12. doi: 10.1016/j.cub.2009.11.022 20060297

24. Selcen D, Muntoni F, Burton BK, Pegoraro E, Sewry C, Bite AV, et al. Mutation in BAG3 causes severe dominant childhood muscular dystrophy. Ann Neurol. 2009;65(1):83–9. Epub 2008/12/17. doi: 10.1002/ana.21553 19085932

25. Odgerel Z, Sarkozy A, Lee HS, McKenna C, Rankin J, Straub V, et al. Inheritance patterns and phenotypic features of myofibrillar myopathy associated with a BAG3 mutation. Neuromuscular disorders: NMD. 2010;20(7):438–42. Epub 2010/07/08. doi: 10.1016/j.nmd.2010.05.004 20605452

26. Ingham RJ, Colwill K, Howard C, Dettwiler S, Lim CS, Yu J, et al. WW domains provide a platform for the assembly of multiprotein networks. Mol Cell Biol. 2005;25(16):7092–106. Epub 2005/08/02. 16055720

27. Li SS. Specificity and versatility of SH3 and other proline-recognition domains: structural basis and implications for cellular signal transduction. Biochem J. 2005;390(Pt 3):641–53. Epub 2005/09/02. 16134966

28. Iwasaki M, Tanaka R, Hishiya A, Homma S, Reed JC, Takayama S. BAG3 directly associates with guanine nucleotide exchange factor of Rap1, PDZGEF2, and regulates cell adhesion. Biochem Biophys Res Commun. 2010;400(3):413–8. Epub 2010/08/31. doi: 10.1016/j.bbrc.2010.08.092 20800573

29. Kassis JN, Virador VM, Guancial EA, Kimm D, Ho AS, Mishra M, et al. Genomic and phenotypic analysis reveals a key role for CCN1 (CYR61) in BAG3-modulated adhesion and invasion. The Journal of pathology. 2009;218(4):495–504. Epub 2009/04/30. doi: 10.1002/path.2557 19402132

30. Kassis JN, Guancial EA, Doong H, Virador V, Kohn EC. CAIR-1/BAG-3 modulates cell adhesion and migration by downregulating activity of focal adhesion proteins. Exp Cell Res. 2006;312(15):2962–71. Epub 2006/07/25. 16859681

31. Kunda P, Baum B. The actin cytoskeleton in spindle assembly and positioning. Trends Cell Biol. 2009;19(4):174–9. Epub 2009/03/17. doi: 10.1016/j.tcb.2009.01.006 19285869

32. Rao X, Zhang Y, Yi Q, Hou H, Xu B, Chu L, et al. Multiple origins of spontaneously arising micronuclei in HeLa cells: direct evidence from long-term live cell imaging. Mutation research. 2008;646(1–2):41–9. Epub 2008/10/11. doi: 10.1016/j.mrfmmm.2008.09.004 18845170

33. London N, Biggins S. Signalling dynamics in the spindle checkpoint response. Nat Rev Mol Cell Biol. 2014;15(11):736–47. Epub 2014/10/11. doi: 10.1038/nrm3888 25303117

34. Toyoshima F, Nishida E. Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1- and myosin X-dependent manner. EMBO J. 2007;26(6):1487–98. Epub 2007/02/24. 17318179

35. Samora CP, Mogessie B, Conway L, Ross JL, Straube A, McAinsh AD. MAP4 and CLASP1 operate as a safety mechanism to maintain a stable spindle position in mitosis. Nat Cell Biol. 2011;13(9):1040–50. Epub 2011/08/09. doi: 10.1038/ncb2297 21822276

36. Ferreira JG, Pereira AJ, Akhmanova A, Maiato H. Aurora B spatially regulates EB3 phosphorylation to coordinate daughter cell adhesion with cytokinesis. J Cell Biol. 2013;201(5):709–24. Epub 2013/05/29. doi: 10.1083/jcb.201301131 23712260

37. Colvin TA, Gabai VL, Gong J, Calderwood SK, Li H, Gummuluru S, et al. Hsp70-Bag3 interactions regulate cancer-related signaling networks. Cancer Res. 2014. Epub 2014/07/06.

38. Fuchs M, Poirier DJ, Seguin SJ, Lambert H, Carra S, Charette SJ, et al. Identification of the key structural motifs involved in HspB8/HspB6-Bag3 interaction. Biochem J. 2010;425(1):245–55. Epub 2009/10/23.

39. Doong H, Vrailas A, Kohn EC. What's in the 'BAG'?—A functional domain analysis of the BAG-family proteins. Cancer letters. 2002;188(1–2):25–32. Epub 2002/10/31. 12406544

40. Doong H, Price J, Kim YS, Gasbarre C, Probst J, Liotta LA, et al. CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70. Oncogene. 2000;19(38):4385–95. Epub 2000/09/12. 10980614

41. Antoku K, Maser RS, Scully WJ Jr., Delach SM, Johnson DE. Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein. Biochem Biophys Res Commun. 2001;286(5):1003–10. Epub 2001/08/31. 11527400

42. Fontanella B, Birolo L, Infusini G, Cirulli C, Marzullo L, Pucci P, et al. The co-chaperone BAG3 interacts with the cytosolic chaperonin CCT: new hints for actin folding. The international journal of biochemistry & cell biology. 2010;42(5):641–50. Epub 2009/12/19.

43. Gentilella A, Khalili K. BAG3 expression in glioblastoma cells promotes accumulation of ubiquitinated clients in an Hsp70-dependent manner. J Biol Chem. 2011;286(11):9205–15. Epub 2011/01/15. doi: 10.1074/jbc.M110.175836 21233200

44. Vassilev LT, Tovar C, Chen S, Knezevic D, Zhao X, Sun H, et al. Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1. Proc Natl Acad Sci U S A. 2006;103(28):10660–5. Epub 2006/07/05. 16818887

45. Gamerdinger M, Hajieva P, Kaya AM, Wolfrum U, Hartl FU, Behl C. Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3. Embo J. 2009;28(7):889–901. doi: 10.1038/emboj.2009.29 19229298

46. Bjorkoy G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A, et al. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol. 2005;171(4):603–14. Epub 2005/11/16. 16286508

47. Komatsu M, Waguri S, Koike M, Sou YS, Ueno T, Hara T, et al. Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell. 2007;131(6):1149–63. Epub 2007/12/18. 18083104

48. Korolchuk VI, Mansilla A, Menzies FM, Rubinsztein DC. Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates. Mol Cell. 2009;33(4):517–27. Epub 2009/03/03. doi: 10.1016/j.molcel.2009.01.021 19250912

49. Rogov V, Dotsch V, Johansen T, Kirkin V. Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. Mol Cell. 2014;53(2):167–78. Epub 2014/01/28. doi: 10.1016/j.molcel.2013.12.014 24462201

50. Linares JF, Amanchy R, Greis K, Diaz-Meco MT, Moscat J. Phosphorylation of p62 by cdk1 controls the timely transit of cells through mitosis and tumor cell proliferation. Mol Cell Biol. 2011;31(1):105–17. Epub 2010/10/27. doi: 10.1128/MCB.00620-10 20974803

51. Yan J, Seibenhener ML, Calderilla-Barbosa L, Diaz-Meco MT, Moscat J, Jiang J, et al. SQSTM1/p62 interacts with HDAC6 and regulates deacetylase activity. PloS one. 2013;8(9):e76016. Epub 2013/10/03. doi: 10.1371/journal.pone.0076016 24086678

52. Ulbricht A, Arndt V, Hohfeld J. Chaperone-assisted proteostasis is essential for mechanotransduction in mammalian cells. Communicative & integrative biology. 2013;6(4):e24925. Epub 2013/08/30.

53. Stevermann L, Liakopoulos D. Molecular mechanisms in spindle positioning: structures and new concepts. Curr Opin Cell Biol. 2012;24(6):816–24. Epub 2012/11/13. doi: 10.1016/j.ceb.2012.10.005 23142476

54. Almonacid M, Terret ME, Verlhac MH. Actin-based spindle positioning: new insights from female gametes. J Cell Sci. 2014;127(Pt 3):477–83. Epub 2014/01/15. doi: 10.1242/jcs.142711 24413163

55. Lancaster OM, Baum B. Might makes right: Using force to align the mitotic spindle. Nat Cell Biol. 2011;13(7):736–8. Epub 2011/07/05. doi: 10.1038/ncb0711-736 21725285

56. Fink J, Carpi N, Betz T, Betard A, Chebah M, Azioune A, et al. External forces control mitotic spindle positioning. Nat Cell Biol. 2011;13(7):771–8. Epub 2011/06/15. doi: 10.1038/ncb2269 21666685

57. Maddox AS, Burridge K. RhoA is required for cortical retraction and rigidity during mitotic cell rounding. J Cell Biol. 2003;160(2):255–65. Epub 2003/01/23. 12538643

58. Kunda P, Pelling AE, Liu T, Baum B. Moesin controls cortical rigidity, cell rounding, and spindle morphogenesis during mitosis. Curr Biol. 2008;18(2):91–101. Epub 2008/01/22. doi: 10.1016/j.cub.2007.12.051 18207738

59. Cramer LP, Mitchison TJ. Myosin is involved in postmitotic cell spreading. J Cell Biol. 1995;131(1):179–89. Epub 1995/10/01. 7559774

60. Pasternack MS, Eisen HN. A novel serine esterase expressed by cytotoxic T lymphocytes. Nature. 1985;314(6013):743–5. Epub 1985/04/01. 3873011

61. Larson SM, Lee HJ, Hung PH, Matthews LM, Robinson DN, Evans JP. Cortical mechanics and meiosis II completion in mammalian oocytes are mediated by myosin-II and Ezrin-Radixin-Moesin (ERM) proteins. Mol Biol Cell. 2010;21(18):3182–92. Epub 2010/07/28. doi: 10.1091/mbc.E10-01-0066 20660156

62. Ulbricht A, Hohfeld J. Tension-induced autophagy: may the chaperone be with you. Autophagy. 2013;9(6):920–2. Epub 2013/03/23. doi: 10.4161/auto.24213 23518596

63. Vos MJ, Zijlstra MP, Kanon B, van Waarde-Verhagen MA, Brunt ER, Oosterveld-Hut HM, et al. HSPB7 is the most potent polyQ aggregation suppressor within the HSPB family of molecular chaperones. Human molecular genetics. 2010;19(23):4677–93. Epub 2010/09/17. doi: 10.1093/hmg/ddq398 20843828

64. During RL, Gibson BG, Li W, Bishai EA, Sidhu GS, Landry J, et al. Anthrax lethal toxin paralyzes actin-based motility by blocking Hsp27 phosphorylation. Embo J. 2007;26(9):2240–50. Epub 2007/04/21. 17446863

65. Werner A, Disanza A, Reifenberger N, Habeck G, Becker J, Calabrese M, et al. SCFFbxw5 mediates transient degradation of actin remodeller Eps8 to allow proper mitotic progression. Nat Cell Biol. 2013;15(2):179–88. Epub 2013/01/15. doi: 10.1038/ncb2661 23314863

66. Eskelinen EL, Prescott AR, Cooper J, Brachmann SM, Wang L, Tang X, et al. Inhibition of autophagy in mitotic animal cells. Traffic. 2002;3(12):878–93. Epub 2002/11/28. 12453151

67. Furuya T, Kim M, Lipinski M, Li J, Kim D, Lu T, et al. Negative regulation of Vps34 by Cdk mediated phosphorylation. Mol Cell. 2010;38(4):500–11. Epub 2010/06/02. doi: 10.1016/j.molcel.2010.05.009 20513426

68. Nakayama Y, Matsui Y, Takeda Y, Okamoto M, Abe K, Fukumoto Y, et al. c-Src but not Fyn promotes proper spindle orientation in early prometaphase. J Biol Chem. 2012;287(30):24905–15. Epub 2012/06/13. doi: 10.1074/jbc.M112.341578 22689581

69. Brunton VG, Frame MC. Src and focal adhesion kinase as therapeutic targets in cancer. Curr Opin Pharmacol. 2008;8(4):427–32. Epub 2008/07/16. doi: 10.1016/j.coph.2008.06.012 18625340

70. Rea SL, Walsh JP, Layfield R, Ratajczak T, Xu J. New insights into the role of sequestosome 1/p62 mutant proteins in the pathogenesis of Paget's disease of bone. Endocrine reviews. 2013;34(4):501–24. Epub 2013/04/25. doi: 10.1210/er.2012-1034 23612225

71. Moscat J, Diaz-Meco MT. p62: a versatile multitasker takes on cancer. Trends Biochem Sci. 2012;37(6):230–6. Epub 2012/03/20. doi: 10.1016/j.tibs.2012.02.008 22424619

72. Yan J. Interplay between HDAC6 and its interacting partners: essential roles in the aggresome-autophagy pathway and neurodegenerative diseases. DNA and cell biology. 2014;33(9):567–80. Epub 2014/06/17. doi: 10.1089/dna.2013.2300 24932665

73. Zhang X, Yuan Z, Zhang Y, Yong S, Salas-Burgos A, Koomen J, et al. HDAC6 modulates cell motility by altering the acetylation level of cortactin. Mol Cell. 2007;27(2):197–213. Epub 2007/07/24. 17643370

74. Zhang Y, Li N, Caron C, Matthias G, Hess D, Khochbin S, et al. HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo. EMBO J. 2003;22(5):1168–79. Epub 2003/02/28. 12606581

75. Sandilands E, Cans C, Fincham VJ, Brunton VG, Mellor H, Prendergast GC, et al. RhoB and actin polymerization coordinate Src activation with endosome-mediated delivery to the membrane. Dev Cell. 2004;7(6):855–69. 15572128

76. Landry MC, Champagne C, Boulanger MC, Jette A, Fuchs M, Dziengelewski C, et al. A Functional Interplay between the Small GTPase Rab11a and Mitochondria-shaping Proteins Regulates Mitochondrial Positioning and Polarization of the Actin Cytoskeleton Downstream of Src Family Kinases. J Biol Chem. 2014;289(4):2230–49. Epub 2013/12/05. doi: 10.1074/jbc.M113.516351 24302731

77. Graham FL, Smiley J, Russell WC, Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol. 1977;36(1):59–74. 886304

78. Jones HW Jr., McKusick VA, Harper PS, Wuu KD. George Otto Gey. (1899–1970). The HeLa cell and a reappraisal of its origin. Obstet Gynecol. 1971;38(6):945–9.

79. Shi Q, King RW. Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines. Nature. 2005;437(7061):1038–42. Epub 2005/10/14. 16222248

80. Klebig C, Korinth D, Meraldi P. Bub1 regulates chromosome segregation in a kinetochore-independent manner. J Cell Biol. 2009;185(5):841–58. Epub 2009/06/03. doi: 10.1083/jcb.200902128 19487456

81. Jakobsen L, Schroder JM, Larsen KM, Lundberg E, Andersen JS. Centrosome isolation and analysis by mass spectrometry-based proteomics. Methods Enzymol. 2013;525:371–93. Epub 2013/03/26. doi: 10.1016/B978-0-12-397944-5.00018-3 23522479

82. Champagne C, Landry MC, Gingras MC, Lavoie JN. Activation of adenovirus type 2 early region 4 ORF4 cytoplasmic death function by direct binding to Src kinase domain. J Biol Chem. 2004;279(24):25905–15. 15070897

83. Lavoie JN, Champagne C, Gingras MC, Robert A. Adenovirus E4 open reading frame 4-induced apoptosis involves dysregulation of src family kinases. J Cell Biol. 2000;150(5):1037–56. 10973994