The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지
DOI QR코드

DOI QR Code

Effect of BIS depletion on HSF1-dependent transcriptional activation in A549 non-small cell lung cancer cells

  • Yun, Hye Hyeon (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Baek, Ji-Ye (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Seo, Gwanwoo (The Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea) ;
  • Kim, Yong Sam (Genome Editing Research Center, KRIBB) ;
  • Ko, Jeong-Heon (Genome Editing Research Center, KRIBB) ;
  • Lee, Jeong-Hwa (Department of Biochemistry, College of Medicine, The Catholic University of Korea)
  • Received : 2018.04.10
  • Accepted : 2018.05.01
  • Published : 2018.07.01
Download PDF
⟨ Previous Next ⟩

Abstract

The expression of BCL-2 interacting cell death suppressor (BIS), an anti-stress or anti-apoptotic protein, has been shown to be regulated at the transcriptional level by heat shock factor 1 (HSF1) upon various stresses. Recently, HSF1 was also shown to bind to BIS, but the significance of these protein-protein interactions on HSF1 activity has not been fully defined. In the present study, we observed that complete depletion of BIS using a CRISPR/Cas9 system in A549 non-small cell lung cancer did not affect the induction of heat shock protein (HSP) 70 and HSP27 mRNAs under various stress conditions such as heat shock, proteotoxic stress, and oxidative stress. The lack of a functional association of BIS with HSF1 activity was also demonstrated by transient downregulation of BIS by siRNA in A549 and U87 glioblastoma cells. Endogenous BIS mRNA levels were significantly suppressed in BIS knockout (KO) A549 cells compared to BIS wild type (WT) A549 cells at the constitutive and inducible levels. The promoter activities of BIS and HSP70 as well as the degradation rate of BIS mRNA were not influenced by depletion of BIS. In addition, the expression levels of the mutant BIS construct, in which 14 bp were deleted as in BIS-KO A549 cells, were not different from those of the WT BIS construct, indicating that mRNA stability was not the mechanism for autoregulation of BIS. Our results suggested that BIS was not required for HSF1 activity, but was required for its own expression, which involved an HSF1-independent pathway.

Keywords

References

  1. 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;18:6183-6190. https://doi.org/10.1038/sj.onc.1203043
  2. Takayama S, Xie Z, Reed JC. An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators. J Biol Chem. 1999;274:781-786. https://doi.org/10.1074/jbc.274.2.781
  3. Rosati A, Graziano V, De Laurenzi V, Pascale M, Turco MC. BAG3: a multifaceted protein that regulates major cell pathways. Cell Death Dis. 2011;2:e141. https://doi.org/10.1038/cddis.2011.24
  4. Rosati A, Ammirante M, Gentilella A, Basile A, Festa M, Pascale M, Marzullo L, Belisario MA, Tosco A, Franceschelli S, Moltedo O, Pagliuca G, Lerose R, Turco MC. Apoptosis inhibition in cancer cells: a novel molecular pathway that involves BAG3 protein. Int J Biochem Cell Biol. 2007;39:1337-1342. https://doi.org/10.1016/j.biocel.2007.03.007
  5. Zhu H, Liu P, Li J. BAG3: a new therapeutic target of human cancers? Histol Histopathol. 2012;27:257-261.
  6. Selcen D, Muntoni F, Burton BK, Pegoraro E, Sewry C, Bite AV, Engel AG. Mutation in BAG3 causes severe dominant childhood muscular dystrophy. Ann Neurol. 2009;65:83-89.
  7. Odgerel Z, Sarkozy A, Lee HS, McKenna C, Rankin J, Straub V, Lochmuller H, Paola F, D'Amico A, Bertini E, Bushby K, Goldfarb LG. Inheritance patterns and phenotypic features of myofibrillar myopathy associated with a BAG3 mutation. Neuromuscul Disord. 2010;20:438-442. https://doi.org/10.1016/j.nmd.2010.05.004
  8. Lei Z, Brizzee C, Johnson GV. BAG3 facilitates the clearance of endogenous tau in primary neurons. Neurobiol Aging. 2015;36:241-248. https://doi.org/10.1016/j.neurobiolaging.2014.08.012
  9. Seidel K, Vinet J, Dunnen WF, Brunt ER, Meister M, Boncoraglio A, Zijlstra MP, Boddeke HW, Rub U, Kampinga HH, Carra S. The HSPB8-BAG3 chaperone complex is upregulated in astrocytes in the human brain affected by protein aggregation diseases. Neuropathol Appl Neurobiol. 2012;38:39-53. https://doi.org/10.1111/j.1365-2990.2011.01198.x
  10. Merabova N, Sariyer IK, Saribas AS, Knezevic T, Gordon J, Turco MC, Rosati A, Weaver M, Landry J, Khalili K. WW domain of BAG3 is required for the induction of autophagy in glioma cells. J Cell Physiol. 2015;230:831-841. https://doi.org/10.1002/jcp.24811
  11. Behl C. Breaking BAG: the Co-Chaperone BAG3 in health and disease. Trends Pharmacol Sci. 2016;37:672-688. https://doi.org/10.1016/j.tips.2016.04.007
  12. Rosati A, Basile A, Falco A, d'Avenia M, Festa M, Graziano V, De Laurenzi V, Arra C, Pascale M, Turco MC. Role of BAG3 protein in leukemia cell survival and response to therapy. Biochim Biophys Acta. 2012;1826:365-369.
  13. Wang HQ, Liu HM, Zhang HY, Guan Y, Du ZX. Transcriptional upregulation of BAG3 upon proteasome inhibition. Biochem Biophys Res Commun. 2008;365:381-385. https://doi.org/10.1016/j.bbrc.2007.11.001
  14. Rosati A, Leone A, Del Valle L, Amini S, Khalili K, Turco MC. Evidence for BAG3 modulation of HIV-1 gene transcription. J Cell Physiol. 2007;210:676-683. https://doi.org/10.1002/jcp.20865
  15. Gentilella A, Khalili K. BAG3 expression is sustained by FGF2 in neural progenitor cells and impacts cell proliferation. Cell Cycle. 2010;9:4245-4247. https://doi.org/10.4161/cc.9.20.13517
  16. Liu J, Qu CB, Xue YX, Li Z, Wang P, Liu YH. MiR-143 enhances the antitumor activity of shikonin by targeting BAG3 expression in human glioblastoma stem cells. Biochem Biophys Res Commun. 2015;468:105-112. https://doi.org/10.1016/j.bbrc.2015.10.153
  17. Flum M, Kleemann M, Schneider H, Weis B, Fischer S, Handrick R, Otte K. miR-217-5p induces apoptosis by directly targeting PRKCI, BAG3, ITGAV and MAPK1 in colorectal cancer cells. J Cell Commun Signal. 2018;12:451-466. https://doi.org/10.1007/s12079-017-0410-x
  18. d'Avenia M, Citro R, De Marco M, Veronese A, Rosati A, Visone R, Leptidis S, Philippen L, Vitale G, Cavallo A, Silverio A, Prota C, Gravina P, De Cola A, Carletti E, Coppola G, Gallo S, Provenza G, Bossone E, Piscione F, Hahne M, De Windt LJ, Turco MC, De Laurenzi V. A novel miR-371a-5p-mediated pathway, leading to BAG3 upregulation in cardiomyocytes in response to epinephrine, is lost in Takotsubo cardiomyopathy. Cell Death Dis. 2015;6:e1948. https://doi.org/10.1038/cddis.2015.280
  19. Ben Aicha S, Lessard J, Pelletier M, Fournier A, Calvo E, Labrie C. Transcriptional profiling of genes that are regulated by the endoplasmic reticulum-bound transcription factor AIbZIP/CREB3L4 in prostate cells. Physiol Genomics. 2007;31:295-305. https://doi.org/10.1152/physiolgenomics.00097.2007
  20. Gentilella A, Passiatore G, Deshmane S, Turco MC, Khalili K. Activation of BAG3 by Egr-1 in response to FGF-2 in neuroblastoma cells. Oncogene. 2008;27:5011-5018. https://doi.org/10.1038/onc.2008.142
  21. Cesaro E, Montano G, Rosati A, Crescitelli R, Izzo P, Turco MC, Costanzo P. WT1 protein is a transcriptional activator of the antiapoptotic bag3 gene. Leukemia. 2010;24:1204-1206. https://doi.org/10.1038/leu.2010.68
  22. Song S, Kole S, Precht P, Pazin MJ, Bernier M. Activation of heat shock factor 1 plays a role in pyrrolidine dithiocarbamate-mediated expression of the co-chaperone BAG3. Int J Biochem Cell Biol. 2010;42:1856-1863. https://doi.org/10.1016/j.biocel.2010.07.021
  23. Yoo HJ, Im CN, Youn DY, Yun HH, Lee JH. Bis is induced by oxidative stress via activation of HSF1. Korean J Physiol Pharmacol. 2014;18:403-409. https://doi.org/10.4196/kjpp.2014.18.5.403
  24. Jacobs AT, Marnett LJ. HSF1-mediated BAG3 expression attenuates apoptosis in 4-hydroxynonenal-treated colon cancer cells via stabilization of anti-apoptotic Bcl-2 proteins. J Biol Chem. 2009;284:9176-9183. https://doi.org/10.1074/jbc.M808656200
  25. Franceschelli S, Rosati A, Lerose R, De Nicola S, Turco MC, Pascale M. Bag3 gene expression is regulated by heat shock factor 1. J Cell Physiol. 2008;215:575-577. https://doi.org/10.1002/jcp.21397
  26. Gentilella A, Khalili K. Autoregulation of co-chaperone BAG3 gene transcription. J Cell Biochem. 2009;108:1117-1124. https://doi.org/10.1002/jcb.22343
  27. Gentilella A, Khalili K. BAG3 expression in glioblastoma cells promotes accumulation of ubiquitinated clients in an Hsp70-dependent manner. J Biol Chem. 2011;286:9205-9215. https://doi.org/10.1074/jbc.M110.175836
  28. Chen Y, Yang LN, Cheng L, Tu S, Guo SJ, Le HY, Xiong Q, Mo R, Li CY, Jeong JS, Jiang L, Blackshaw S, Bi LJ, Zhu H, Tao SC, Ge F. Bcl2-associated athanogene 3 interactome analysis reveals a new role in modulating proteasome activity. Mol Cell Proteomics. 2013;12:2804-2819. https://doi.org/10.1074/mcp.M112.025882
  29. Dai C, Sampson SB. HSF1: Guardian of proteostasis in cancer. Trends Cell Biol. 2016;26:17-28. https://doi.org/10.1016/j.tcb.2015.10.011
  30. Dai C, Santagata S, Tang Z, Shi J, Cao J, Kwon H, Bronson RT, Whitesell L, Lindquist S. Loss of tumor suppressor NF1 activates HSF1 to promote carcinogenesis. J Clin Invest. 2012;122:3742-3754. https://doi.org/10.1172/JCI62727
  31. Cui MN, Yun HH, Lee NE, Kim HY, Im CN, Kim YS, Lee JH. Depletion of BIS sensitizes A549 cells to treatment with cisplatin. Mol Cell Toxicol. 2016;12:63-71. https://doi.org/10.1007/s13273-016-0009-y
  32. Baek JY, Yun HH, Im CN, Ko JH, Jeong SM, Lee JH. BIS overexpression does not affect the sensitivity of HEK 293T cells against apoptosis. Mol Cell Toxicol. 2017;13:95-103. https://doi.org/10.1007/s13273-017-0010-0
  33. Jelluma N, Yang X, Stokoe D, Evan GI, Dansen TB, Haas-Kogan DA. Glucose withdrawal induces oxidative stress followed by apoptosis in glioblastoma cells but not in normal human astrocytes. Mol Cancer Res. 2006;4:319-330. https://doi.org/10.1158/1541-7786.MCR-05-0061
  34. Liu Y, Song XD, Liu W, Zhang TY, Zuo J. Glucose deprivation induces mitochondrial dysfunction and oxidative stress in PC12 cell line. J Cell Mol Med. 2003;7:49-56. https://doi.org/10.1111/j.1582-4934.2003.tb00202.x
  35. Schweingruber C, Rufener SC, Zund D, Yamashita A, Muhlemann O. Nonsense-mediated mRNA decay - mechanisms of substrate mRNA recognition and degradation in mammalian cells. Biochim Biophys Acta. 2013;1829:612-623. https://doi.org/10.1016/j.bbagrm.2013.02.005
  36. Karousis ED, Nasif S, Muhlemann O. Nonsense-mediated mRNA decay: novel mechanistic insights and biological impact. Wiley Interdiscip Rev RNA. 2016;7:661-682. https://doi.org/10.1002/wrna.1357
  37. Kim HY, Kim YS, Yun HH, Im CN, Ko JH, Lee JH. ERK-mediated phosphorylation of BIS regulates nuclear translocation of HSF1 under oxidative stress. Exp Mol Med. 2016;48:e260. https://doi.org/10.1038/emm.2016.84
  38. Jin YH, Ahn SG, Kim SA. BAG3 affects the nucleocytoplasmic shuttling of HSF1 upon heat stress. Biochem Biophys Res Commun. 2015;464:561-567. https://doi.org/10.1016/j.bbrc.2015.07.006
  39. Im CN, Yun HH, Lee JH. Heat shock factor 1 depletion sensitizes A172 glioblastoma cells to temozolomide via suppression of cancer stem cell-like properties. Int J Mol Sci. 2017;18:E468. https://doi.org/10.3390/ijms18020468
  40. Fang X, Bogomolovas J, Wu T, Zhang W, Liu C, Veevers J, Stroud MJ, Zhang Z, Ma X, Mu Y, Lao DH, Dalton ND, Gu Y, Wang C, Wang M, Liang Y, Lange S, Ouyang K, Peterson KL, Evans SM, Chen J. Loss-of-function mutations in co-chaperone BAG3 destabilize small HSPs and cause cardiomyopathy. J Clin Invest. 2017;127:3189-3200. https://doi.org/10.1172/JCI94310
  41. Li J, Labbadia J, Morimoto RI. Rethinking HSF1 in stress, development, and organismal health. Trends Cell Biol. 2017;27:895-905. https://doi.org/10.1016/j.tcb.2017.08.002
  42. Su KH, Dai C. Metabolic control of the proteotoxic stress response: implications in diabetes mellitus and neurodegenerative disorders. Cell Mol Life Sci. 2016;73:4231-4248. https://doi.org/10.1007/s00018-016-2291-1
  43. Jiang S, Tu K, Fu Q, Schmitt DC, Zhou L, Lu N, Zhao Y. Multifaceted roles of HSF1 in cancer. Tumour Biol. 2015;36:4923-4931. https://doi.org/10.1007/s13277-015-3674-x
  44. Mendillo ML, Santagata S, Koeva M, Bell GW, Hu R, Tamimi RM, Fraenkel E, Ince TA, Whitesell L, Lindquist S. HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers. Cell. 2012;150:549-562. https://doi.org/10.1016/j.cell.2012.06.031
  45. Dai C, Whitesell L, Rogers AB, Lindquist S. Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell. 2007;130:1005-1018. https://doi.org/10.1016/j.cell.2007.07.020