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Dynamics of Heat Shock Proteins in Immunity and Aging

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Heat Shock Proteins in Signaling Pathways

Part of the book series: Heat Shock Proteins ((HESP,volume 17))

Abstract

Heat Shock Proteins (HSP) are one of the classical molecules that regulate cellular homeostasis. HSP play multifunctional roles that are crucial for folding/unfolding of proteins, cell-cycle control and signaling, and protection of cells against stress/apoptosis. HSP have also been implicated in antigen presentation with the role of chaperoning and transferring antigenic peptides and providing immunity. HSP have been referred as molecular chaperones since they assist in the repair of denatured proteins or promote their degradation after stress or injury. Moreover, HSP are likely to have anti-apoptotic properties and have been reported to be significantly elevated in a plethora of human cancers. The increase in expression levels of HSP has been robustly related with therapeutic resistance and poor survival. The immunological functions and prospective immunological repertoire of HSP put them in critical position that serves as important therapeutic implications for specific drug targets. In this chapter, we have discussed on the existing scientific data about HSP with an effort to highlight the possible future implication of HSP during stress, aging, apoptosis and their status at post-translational and mitochondrial level and the possible drug targets for improving prognosis and treatment of various diseases.

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Abbreviations

HSF:

heat shock factor

HSP:

heat shock proteins

PTM:

post translational modification

RNAi:

ribonucleic acid interference

ROS:

reactive oxygen species

References

  • Balch WE, Morimoto RI, Dillin A, Kelly JW (2008) Adapting proteostasis for disease intervention. Science 319:916–919

    Article  CAS  PubMed  Google Scholar 

  • Beere HM (2005) Death versus survival: functional interaction between the apoptotic and stress-inducible heat shock protein pathways. J Clin Invest 115:2633–2639

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bennett CF, Choi H, Kaeberlein M (2014) Searching for the elusive mitochondrial longevity signal in C. elegans. Worm 3:e959404

    Article  PubMed Central  PubMed  Google Scholar 

  • Caito S, Fretham S, Martinez-Finley E et al (2012) Genome-wide analyses of metal responsive genes in Caenorhabditis elegans. Front Genet 3:52

    Article  PubMed Central  PubMed  Google Scholar 

  • Calderwood SK, Murshid A (2017) Molecular chaperone accumulation in cancer and decrease in Alzheimer’s disease: the potential roles of HSF1. Front Neurosci 11:192

    Article  PubMed Central  PubMed  Google Scholar 

  • Chiang WC, Ching TT, Lee HC, Mousigian C, Hsu AL (2012) HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity. Cell 148:322–324

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cohen E, Bieschke J, Perciavalle RM, Kelly JW, Dillin A (2006) Opposing activities protect against age-onset proteotoxicity. Science 313:1604–1610

    Article  CAS  PubMed  Google Scholar 

  • Crombie TA, Tang L, Choe KP, Julian D (2016) Inhibition of the oxidative stress response by heat stress in Caenorhabditis elegans. J Exp Biol 219:2201–2201

    Article  PubMed  Google Scholar 

  • Durai S, Singh N, Kundu S, Balamurugan K (2014) Proteomic investigation of Vibrio alginolyticus challenged Caenorhabditis elegans revealed regulation of cellular homeostasis proteins and their role in supporting innate immune system. Proteomics 14:1820–1832

    Article  CAS  PubMed  Google Scholar 

  • Durieux J, Wolff S, Dillin A (2011) The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell 144:79–71

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ezemaduka AN, Wang Y, Li X (2017) Expression of CeHSP17 protein in response to heat shock and heavy metal ions. J Nematol 49:334–340

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Garigan D, Hsu AL, Fraser AG, Kamath RS, Ahringer J, Kenyon C (2002) Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics 161:1101–1112

    CAS  PubMed  PubMed Central  Google Scholar 

  • GuhaThakurta D, Palomar L, Stormo GD et al (2002) Identification of a novel cis-regulatory element involved in the heat shock response in Caenorhabditis elegans using microarray gene expression and computational methods. Genome Res 12:701–712

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hajdu-Cronin YM, Chen WJ, Sternberg PW (2004) The L-type cyclin CYL-1 and the heat-shock-factor HSF-1 are required for heat-shock-induced protein expression in Caenorhabditis elegans. Genetics 168:1937–1949

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Henze A, Homann T, Rohn I et al (2016) Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin. Sci Rep 6:37346

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300:1142–1145

    Article  CAS  PubMed  Google Scholar 

  • Jaattela M (1999) Heat shock proteins as cellular lifeguards. Ann Med 31:261–261

    Article  CAS  PubMed  Google Scholar 

  • JebaMercy G, Durai S, Prithika U et al (2016) Role of DAF-21 protein in Caenorhabditis elegans immunity against Proteus mirabilis infection. J Proteome 145:81–90

    Article  CAS  Google Scholar 

  • Jovaisaite V, Mouchiroud L, Auwerx J (2014) The mitochondrial unfolded protein response, a conserved stress response pathway with implications in health and disease. J Exp Biol 217:137–133

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kaletta T, Hengartner MO (2006) Finding function in novel targets: C. elegans as a model organism. Nat Rev Drug Discov 5:387–398

    Article  CAS  PubMed  Google Scholar 

  • Kimura K, Tanaka N, Nakamura N, Takano S, Ohkuma S (2007) Knockdown of mitochondrial heat shock protein 70 promotes progeria-like phenotypes in Caenorhabditis elegans. J Biol Chem 282:5910–5918

    Article  CAS  PubMed  Google Scholar 

  • Kumsta C, Chang JT, Schmalz J, Hansen M (2017) Hormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans. Nat Commun 8:14337

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lanneau D, Brunet M, Frisan E, Solary E, Fontenay M, Garrido C (2008) Heat shock proteins: essential proteins for apoptosis regulation. J Cell Mol Med 12:743–761

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li Z, Srivastava P (2004) Heat-shock proteins. Curr Protoc Immunol Appendix 1:Appendix 1T https://doi.org/10.1002/0471142735.ima01ts58

  • Li F, Huang Y, Huang YY et al (2017) MicroRNA-146a promotes IgE class switch in B cells via upregulating 14-3-3sigma expression. Mol Immunol 92:180–189

    Article  CAS  PubMed  Google Scholar 

  • Lindquist S, Craig EA (1988) The heat-shock proteins. Annu Rev Genet 22:631–677

    Article  CAS  PubMed  Google Scholar 

  • Link CD, Cypser JR, Johnson CJ, Johnson TE (1999) Direct observation of stress response in Caenorhabditis elegans using a reporter transgene. Cell Stress Chaperones 4:235–232

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liu Y, Samuel BS, Breen PC, Ruvkun G (2014) Caenorhabditis elegans pathways that surveil and defend mitochondria. Nature 508:406–410

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Marcus A, Gowen BG, Thompson TW et al (2014) Recognition of tumors by the innate immune system and natural killer cells. Adv Immunol 122:91–128

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Melo JA, Ruvkun G (2012) Inactivation of conserved C. elegans genes engages pathogen- and xenobiotic-associated defenses. Cell 149:452–466

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mohri-Shiomi A, Garsin DA (2008) Insulin signaling and the heat shock response modulate protein homeostasis in the Caenorhabditis elegans intestine during infection. J Biol Chem 283:194–191

    Article  CAS  PubMed  Google Scholar 

  • Morimoto RI (1998) Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 12:3788–3786

    Article  CAS  PubMed  Google Scholar 

  • Morimoto RI (2008) Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging. Genes Dev 22(11):1427–1438

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Morley JF, Morimoto RI (2004) Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell 15:657–654

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Morrison JK, Friday AJ, Henderson MA, Hao E, Keiper BD (2014) Induction of cap-independent BiP (hsp-3) and Bcl-2 (ced-9) translation in response to eIF4G (IFG-1) depletion in C. elegans. Translation (Austin) 2:e28935

    PubMed Central  Google Scholar 

  • Morton EA, Lamitina T (2013) Caenorhabditis elegans HSF-1 is an essential nuclear protein that forms stress granule-like structures following heat shock. Aging Cell 12:112–112

    Article  CAS  PubMed  Google Scholar 

  • Munkacsy E, Rea SL (2014) The paradox of mitochondrial dysfunction and extended longevity. Exp Gerontol 56:221–233

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Palazon A, Tyrakis PA, Macias D et al (2017) An HIF-1alpha/VEGF-A axis in cytotoxic T cells regulates tumor progression. Cancer Cell 32:669–683

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Park SK, Tedesco PM, Johnson TE (2009) Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1. Aging Cell 8:258–269

    Article  CAS  PubMed  Google Scholar 

  • Prithika U, Deepa V, Balamurugan K (2016) External induction of heat shock stimulates the immune response and longevity of Caenorhabditis elegans towards pathogen exposure. Innate Immun 22:466–478

    Article  CAS  PubMed  Google Scholar 

  • Qian H, Xu X, Niklason LE (2015) Bmk-1 regulates lifespan in Caenorhabditis elegans by activating hsp-16. Oncotarget 6:18790–18799

    PubMed  PubMed Central  Google Scholar 

  • Riddle DL, Albert PS (1997) Genetic and environmental regulation of dauer larva development. Cold Spring Harbor Laboratory, Cold Spring Harbor

    Google Scholar 

  • Ritossa F (1962) A new puffing pattern induced by temperature shock and DNP in Drosophila. Exp Dermatol 18:571–573

    CAS  Google Scholar 

  • Roh JY, Lee J, Choi J (2006) Assessment of stress-related gene expression in the heavy metal-exposed nematode Caenorhabditis elegans: a potential biomarker for metal-induced toxicity monitoring and environmental risk assessment. Environ Toxicol Chem 25:2946–2946

    Article  CAS  PubMed  Google Scholar 

  • Shojadoost B, Kulkarni RR, Brisbin JT, Quinteiro-Filho W, Alkie TN, Sharif S (2017) Interactions between lactobacilli and chicken macrophages induce antiviral responses against avian influenza virus. Res Vet Sci. https://doi.org/10.1016/j.rvsc.2017.10.007

  • Singh V, Aballay A (2006) Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity. Proc Natl Acad Sci U S A 103:13092–13097

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tower J (2009) HSP and aging. Trends Endocrinol Metab 20:216–212

    Article  CAS  PubMed  Google Scholar 

  • Truttmann MC, Cruz VE, Guo X, Engert C, Schwartz TU, Ploegh HL (2016) The Caenorhabditis elegans protein FIC-1 is an AMPylase that covalently modifies heat-shock 70 family proteins, translation elongation factors and histones. PLoS Genet 12:e1006023

    Article  PubMed Central  PubMed  Google Scholar 

  • Voellmy R (2004) On mechanisms that control heat shock transcription factor activity in metazoan cells. Cell Stress Chaperones 9:122–133

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Walker GA, Lithgow GJ (2003) Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin-like signals. Aging Cell 2:131–139

    Article  CAS  PubMed  Google Scholar 

  • Walker GA, White TM, McColl G et al (2001) Heat shock protein accumulation is upregulated in a long-lived mutant of Caenorhabditis elegans. J Gerontol A Biol Sci Med Sci 56:B281–B287

    Article  CAS  PubMed  Google Scholar 

  • Wu C (1995) Heat shock transcription factors: structure and regulation. Annu Rev Cell Dev Biol 11:441–469

    Article  CAS  PubMed  Google Scholar 

  • Yokoyama K, Fukumoto K, Murakami T et al (2002) Extended longevity of Caenorhabditis elegans by knocking in extra copies of hsp70F, a homolog of mot-2 (mortalin)/mthsp70/Grp75. FEBS Lett 516:53–57

    Article  CAS  PubMed  Google Scholar 

  • Yuan J, Horvitz HR (2004) A first insight into the molecular mechanisms of apoptosis. Cell 116:S53–S56

    Article  CAS  PubMed  Google Scholar 

  • Zevian SC, Yanowitz JL (2014) Methodological considerations for heat shock of the nematode Caenorhabditis elegans. Methods 68:450–457

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhou KI, Pincus Z, Slack FJ (2011) Longevity and stress in Caenorhabditis elegans. Aging (Albany NY) 3:733–753

    Article  Google Scholar 

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Acknowledgements

Dr. K. Balamurugan acknowledges the DST-SERC Fast Track Young Scientist Scheme (No. SR/FT/LS-83/2009 (G)), DST (SERB) (No. SR/SO/AS-80/2010), DBT (BT/PR14932/MED/29/233/2010), ICMR (Sanction No: 5/3/3/13/2010-ECD-I), UGC Major Research Project (No. 42-222/2013 (SR) and CSIR (No. 37(1460)/11/EMR-II), DST- FIST (Grant No. SRFST/ LSI-087/2008), PURSE (Grant No. SR/S9Z-23/2010/42(G)) and UGC SAP-DRS-I [Grant No. F.3-28/2011 (SAP-II)], New Delhi, India for financial assistances. Authors gratefully acknowledge the computational and bioinformatics facility provided by the Alagappa University Bioinformatics Infrastructure Facility (funded by DBT, GOI; Grant No. BT/BI/25/015/2012).

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Authors and Affiliations

  1. Department of Biotechnology, Science Campus, Alagappa University, Karaikudi, Tamil Nadu, India

    Udayakumar Prithika & Krishnaswamy Balamurugan

Authors
  1. Udayakumar Prithika
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  2. Krishnaswamy Balamurugan
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Editors and Affiliations

  1. Professor, Department of Medicine and Director, Precision Therapeutics Proteogenomics Diagnostic Center Eleanor N. Dana Cancer Center, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    Alexzander A. A. Asea

  2. Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Punit Kaur

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Prithika, U., Balamurugan, K. (2019). Dynamics of Heat Shock Proteins in Immunity and Aging. In: Asea, A., Kaur, P. (eds) Heat Shock Proteins in Signaling Pathways. Heat Shock Proteins, vol 17. Springer, Cham. https://doi.org/10.1007/978-3-030-03952-3_5

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