Molecular Mechanism and Role of Translational Values of Heat Shock Protein (HSP27) in Various Disease
Journal of Pharmaceutical Research International,
HSP27, also known as HSPB1, was first discovered with a molecular weight 27kDa belonging to the four member gene family. Elevated levels of HSP27 are seen when different unfavorable conditions prevail such as increase in temperature and oxidative stress or exposure to heavy metals or organic solvents. They possess ATP-independent chaperone like activity which helps in maintaining protein homeostasis. It can also form large oligomers (300-600 kDa) containing different numbers of subunits. It is composed of total 205 amino acids. HSP27 undergoes post-translational modifications i.e. phosphorylation thereby converting large oligomers into dimers. It can act as an anti-apoptotic and antioxidant molecule during oxidative stress. The elevated form of HSP27 is also seen in some cancer belongs to breast, ovary, prostate, brain, colorectal, hepatocellular carcinoma, lung, liver, and cervical regions. Keeping in view of molecular roles of HSP27 signaling in various pathways, we have proposed their translational values in different diseases. In addition, we have also reported the existing scientific data on the HSP27 as the potential cancer biomarker and their therapeutic targets for improved prognosis and treatment in different diseases.
- Heat shock protein
How to Cite
Vidyasagar A, Wilson NA, Djamali A. Heat shock protein 27 (HSP27): Biomarker of disease and therapeutic target. Fibrogenesis Tissue Repair. 2012;5:7.
Kim KK, Kim R, Kim SH. Crystal structure of a small heat-shock protein. Nature. 1998;394:595-9.
Lianos GD, Alexiou GA, Mangano A, Mangano A, Rausei S, Boni L, Dionigi G, Roukos DH. The role of heat shock proteins in cancer. Cancer Lett. 2015;360: 114-8.
Trivedi V, Gadhvi P, Chorawala M, Shah G. Role of heat shock proteins in immune response and immunotherapy for human cancer. Int. J. Pharm. Sci. Rev. Res. 2010; 2:57-62.
Sudnitsyna MV, Gusev NB. Methylglyoxal and small heat shock proteins. Biochemistry Moscow. 2017;82:751-759.
Hickey E, Brandon SE, Smale G, Lloyd D, Weber LA. Sequence and regulation of a gene encoding a human 89-kilodalton heat shock protein. Mol. Cell Biol. 1989;9:2615-2626.
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;12:842–846.
Fossa P, Cichero E. In silico evaluation of human small heat shock protein HSP27: homology modeling, mutation analyses and docking studies. Bioorg Med Chem. 2015;23:3215-20.
Rogalla T, Ehrnsperger M, Preville X, Kotlyarov A, Lutsch G, Ducasse C, Paul C, Wieske M, Arrigo AP, Buchner J, Gaestel M. Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor alpha by phosphorylation. J. Biol. Chem. 1999;274:18947-56.
Hino M, Kurogi K, Okubo MA, Murata-Hori M, Hosoya H. Small heat shock protein 27 (HSP27) associates with tubulin/ microtubules in HeLa cells. Biochem. Biophys. Res. Commun. 2000;271:164-9.
Ischia J, Saad F, Gleave M. The promise of heat shock protein inhibitors in the treatment of castration resistant prostate cancer. Curr. Opin. Urol. 2013;23:194- 200.
Ghayour-Mobarhan M, Saber H, Ferns GA. The potential role of heat shock protein 27 in cardiovascular disease. Clin Chim Acta. 2012;413:15-24.
Lindquist S, Craig EA. The heat-shock proteins. Ann. Rev. Gen. 1988;22:631-677.
Han T, Li J, Xue J, Li H, Xu F, Cheng K, Li D, Li Z, Gao M, Hua H. Scutellarin derivatives as apoptosis inducers: Design, synthesis and biological evaluation. Eur. J. Med. Chem. 2017;135:270-281.
Lelj-Garolla B, Mauk AG. Roles of the N- and C-terminal sequences in Hsp27 self-association and chaperone activity. Protein Sci. 2012;21:122-123.
Gusev NB, Bogatcheva NV, Marston SB. Structure and properties of small heat shock proteins (sHsp) and their interaction with cytoskeleton proteins. Biochemistry Moscow. 2002;67:511-9.
Penke B, Bogár F, Crul T, Sántha M, Tóth ME, Vígh L. Heat shock proteins and autophagy pathways in neuroprotection: From molecular bases to pharmacological interventions. Int. J. Mol. Sci. 2018;19:325.
Brunet SM, De Thonel A, Hammann A, Joly AL, Bossis G, Fourmaux E, Bouchot A, Landry J, Piechaczyk M, Garrido C. Heat shock protein 27 is involved in SUMO-2/3 modification of heat shock factor 1 and thereby modulates the transcription factor activity. Oncogene. 2009;28:3332-3344.
Katsogiannou M, Andrieu C, Rocchi P. Heat shock protein 27 phosphorylation state is associated with cancer progression. Front. Genet. 2014;5:346.
Wang X, Chen M, Zhou J, Zhang X. HSP27, 70 and 90, anti-apoptotic proteins, in clinical cancer therapy. Int J Oncol 2014;45:18-30.
Garrido C. Size matters: Of the small HSP27 and its large oligomers. Cell Death Differ. 2002;9:483-485.
Heinrich JC, Donakonda S, Haupt VJ, Lennig P, Zhang Y, Schroeder M. New HSP27 inhibitors efficiently suppress drug resistance development in cancer cells. Oncotarget. 2016;7:68156-68169.
Ghosh A, Lai C, McDonald S, Suraweera N, Sengupta N, Propper D, Dorudi S, Silver A. HSP27 expression in primary colorectal cancers is dependent on mutation of KRAS and PI3K/AKT activation status and is independent of TP53. Exp. Mol. Pathol. 2013;94:103-8.
Liang C, Xu Y, Ge H, Li G, Wu J. The clinicopathological and prognostic value of HSP27 in hepatocellular carcinoma: A systematic review and meta-analysis. Onco. Targets Ther. 2018;11:1293–1303.
Małusecka E, Zborek A, Krzyzowska-Gruca S, Krawczyk Z. Expression of heat shock proteins HSP70 and HSP27 in primary non-small cell lung carcinomas: An immunohistochemical study. Anticancer Res. 2001;21(2A):1015-1021.
Baylot V, Andrieu C, Katsogiannou M, Taieb D, Garcia S, Giusiano S, Acunzo J, Iovanna J, Gleave M, Garrido C, Rocchi P. OGX-427 inhibits tumor progression and enhances gemcitabine chemotherapy in pancreatic cancer. Cell Death Dis. 2011;2:e221.
Feng JT, Liu YK, Song HY, Dai Z, Qin LX, Almofti MR, Fang CY, Lu HJ, Yang PY, Tang ZY. Heat‐shock protein 27: A potential biomarker for hepatocellular carcinoma identified by serum proteome analysis. Proteomics. 2005;5:4581- 4588.
Jin Y, Kim SC, Kim HJ, Ju W, Kim YH, Kim H. Use of protein-based biomarkers of exfoliated cervical cells for primary screening of cervical cancer. Arch. Pharm. Res. 2018;41:438-449.
Guo Y, Ziesch A, Hocke S, Kampmann E, Ochs S, De Toni EN, Göke B, Gallmeier E. Overexpression of heat shock protein 27 (HSP27) increases gemcitabine sensitivity in pancreatic cancer cells through S-phase arrest and apoptosis. J. Cell Mol. Med. 2015;19:340-350.
Sehouli J, Alvarez AM, Manouchehrpour S, Ghatage P, Szczylik C, Zimmermann A, Bauknecht T, Look KY, Oskay-Öezcelik G. A phase II trial of pemetrexed in combination with carboplatin in patients with recurrent ovarian or primary peritoneal cancer. Gynecol. Oncol. 2012;124:205-209.
Pavan S, Musiani D, Torchiaro E, Migliardi G, Gai M, Di Cunto F, Erriquez J, Olivero M, Di Renzo MF. HSP27 is required for invasion and metastasis triggered by hepatocyte growth factor. Int. J. Cancer 2014;134:1289-1299.
Idippily ND, Zheng Q, Gan C, Quamine A, Ashcraft MM, Zhong B, Su B. Copalic acid analogs down-regulate androgen receptor and inhibit small chaperone protein. Bioorg. Med. Chem. Lett. 2017;27:2292-2295.
Azad AA, Zoubeidi A, Gleave ME, Chi KN. Targeting heat shock proteins in metastatic castration-resistant prostate cancer. Nat Rev Urol. 2014;12:26-36.
Banerjee S, Lin CF, Skinner KA, Schiffhauer LM, Peacock J, Hicks DG, Redmond EM, Morrow D, Huston A, Shayne M, Langstein HN, Miller-Graziano CL, Strickland J, O'Donoghue L, De AK. Heat shock protein 27 differentiates tolerogenic macrophages that may support human breast cancer progression. Cancer Res. 2011;71:318-327.
Liu W, Ma Y, Huang L, Peng J, Zhang P, Zhang H, Chen J, Qin H. Identification of HSP27 as a potential tumor marker for colorectal cancer by the two-dimensional polyacrylamide gel electrophoresis. Mol. Biol. Rep. 2009;37: 3207-3216.
Sheng B, Qi C, Liu B, Lin Y, Fu T, Zeng Q. Increased HSP27 correlates with malignant biological behavior of non-small cell lung cancer and predicts patient’s survival. Sci. Rep. 2017;7:13807.
Wang C, Zhang Y, Guo K, Wang N, Jin H, Liu Y, Qin W. Heat shock proteins in hepatocellular carcinoma: Molecular mechanism and therapeutic potential. Int. J. Cancer 2016;138:1824-34.
Weeks SD, Muranova LK, Heirbaut M. Characterization of human small heat shock protein HSPB1 α-crystallin domain localized mutants associated with hereditary motor neuron diseases. Sci. Rep. 2018;8:688.
Paul S, Mahanta S. Association of heat-shock proteins in various neurodegenerative disorders: Is it a master key to open the therapeutic door? Mol. Cell Biochem. 2014;386:45-61.
Evgrafov OV, Mersiyanova I, Irobi J, Van Den Bosch L, Dierick I, Leung CL, Schagina O, Verpoorten N, Van Impe K, Fedotov V, Dadali E, Auer-Grumbach M, Windpassinger C, Wagner K, Mitrovic Z, Hilton-Jones D, Talbot K, Martin JJ, Vasserman N, Tverskaya S, Polyakov A, Liem RK, Gettemans J, Robberecht W, De Jonghe P, Timmerman V. Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. Nat Genet. 2004;36:602-606.
Wu J, Jiang S, Ding Z, Liu L. Role of heat shock protein 27 in cardiovascular disease. J. Biochem. Pharmacol. Res. 2013;1: 43-50.
Somara S, Bitar KN. Tropomyosin interacts with phosphorylated HSP27 in agonist-induced contraction of smooth muscle. Am. J. Physiol. Cell Physiol. 2004;286:C1290-C1301.
Virella G, Lopes-Virella MF. Humoral immunity and atherosclerosis. Nat. Med. 2003;9:243-244.
Soo ET, Yip GW, Lwin ZM, Kumar SD, Bay BH. Heat shock proteins as novel therapeutic targets in cancer. In Vivo 2008;22:311-315.
Asthana A, Bollapalli M, Tangirala R, Bakthisaran R, Rao ChM. HSP27 suppresses the Cu2+-induced amyloidogenicity, redox activity, and cytotoxicity of α-synuclein by metal ion stripping. Free Radic Biol Med. 2014;72: 176-190.
Abstract View: 164 times
PDF Download: 148 times