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Gene Review

Hspa1b  -  heat shock protein 1B

Mus musculus

Synonyms: HSP70.1, HSP70A1, Hcp70.1, Heat shock 70 kDa protein 1, Heat shock 70 kDa protein 1B, ...
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Disease relevance of Hspa1b

  • BACKGROUND: Hspa1a and Hspa1b genes encode stress-inducible 70-kDa heat shock proteins (Hsp70) that protect cells from insults such as ischemia [1].
  • However, little information is available on the antiapoptotic mechanism of HSP70.1 protein after cerebral ischemia [2].
  • Hyperthermia pretreatment not only blocked cerulein-induced trypsinogen activation, pancreatic edema, and vacuolization in Hsp70.1+/+ mice, but also decreased basally elevated trypsin activity in Hsp70.1-/- mice [3].
  • The vaccine consisted of synthetic human Abeta42 covalently cross-linked with DnaK, an Hsp70 homolog of Escherichia coli [4].
  • OBJECTIVES: Heat shock proteins (Hsp's) protect cellular proteins in response to injury, and the role of Hsp70 in experimental pancreatitis was recently described [3].

Psychiatry related information on Hspa1b

  • In this study, we produced an Hsp70-supported vaccine to induce the generation of antibodies against amyloid-beta (Abeta) peptides, the major constituent of beta-amyloid plaques in Alzheimer's disease [4].

High impact information on Hspa1b


Chemical compound and disease context of Hspa1b


Biological context of Hspa1b

  • The detailed analysis of the activity of a luciferase reporter gene under the control of the hsp70.1 promoter, as well as the description of the protein expression patterns of the major heat shock proteins in the central nervous system, show that HSF2 and heat shock protein expression domains do not coincide [14].
  • The mouse HSP70.1 gene, which codes for a heat shock protein (hsp70), is highly transcribed at the onset of zygotic genome activation (ZGA) [15].
  • The promoter of HSP70.1 contains four heat shock element (HSE) boxes which are the binding sites of heat shock transcription factors (HSF) [15].
  • The p38beta MAPK mediated the effects of CO on cytoprotection and Hsp70 regulation [16].
  • Furthermore, when osmotic stress was applied in vivo, hsp70.1-deficient mice exhibited increased apoptosis in the renal medulla [17].

Anatomical context of Hspa1b

  • In this study we demonstrate for the first time that the protective effects of CO involve the increased expression of the 70-kDa inducible heat shock protein (Hsp70) in murine lung endothelial cells and fibroblasts [16].
  • Isolated growing dictyate oocytes also display a nuclear HSF1 localization, but, in contrast with embryos, they transcribe both hsp70.1 and hsp70.3 genes only after heat shock [18].
  • In order to elucidate the functions of constitutive and stress-inducible Hsp70 expression in mouse preimplantation embryos, the consequences of inhibiting expression with antisense oligonucleotides complementary to the mRNAs of hsp70-1 and hsp70-3 (A070-1/3) were evaluated [19].
  • The treatment of the thymus zone resulted in more pronounced changes in the cytokine production as well as in NO and Hsp70 synthesis [20].
  • Here we report that CHIP, an ubiquitin ligase that interacts directly with Hsp70/90, induces ubiquitination of the microtubule associated protein, tau [21].

Associations of Hspa1b with chemical compounds

  • This unfolded protein response is also evident from the dramatic induction of Hsp70 on expression of polyglutamine-expanded protein in the cellular model [22].
  • Conversely, induction of Hsp70 through treatment with either geldanamycin or heat shock factor 1 leads to a decrease in tau steady-state levels and a selective reduction in detergent insoluble tau [21].
  • Our results show that levels of HO activity and expression of inducible Hsp70 and the ratio of GSH/GSSG in the different brain regions examined were positively correlated with the content of peroxides [23].
  • RT-PCR and Western blotting were used to measure the expression of PrP(C) and heat-shock protein (Hsp70) in mouse neuroblastoma (N18) cells cultured 3 hr to 3 days in media deprived of 97.5% (L) or 75% (M) of its glucose [9].
  • Substantia Nigra was the brain area exhibiting the highest levels of HO-2, constitutive and inducible Hsp70, GSSG, peroxides, iron, and calcium, in contrast with the lowest content in GSH, GSH/GSSG ratio and glutathione reductase activity, compared to the other cerebral regions examined [23].

Physical interactions of Hspa1b

  • In this study, we show that Hsp70-peptide complexes (pc) isolated from brains of mice with EAE prevented the development of EAE clinically and pathologically when administered before proteolipid protein 139-151 (PLP139-151) immunization [24].
  • In the absence of ATP from cell extracts, protein kinase activity of Mos was lost within 6 h on ice even though the Mos protein was not degraded and remained bound to Hsp70 [25].

Regulatory relationships of Hspa1b


Other interactions of Hspa1b

  • We show in tumor cells that hypericin targets the heat shock protein (Hsp) 90 chaperone but not Hsp70 (Hsc70) to enhanced ubiquitinylation [30].
  • Suppression of Hsp70 expression and/or genetic deletion of heat shock factor-1, the principle transcriptional regulator of Hsp70, attenuated the cytoprotective and immunomodulatory effects of CO in mouse lung cells and in vivo [16].
  • In contrast, hsp70.1+/+ MEFs exhibited no caspase-9 or caspase-3 activation and finally recovered intact cell morphology when cells were shifted back to an isosmotic state [31].
  • Three Hsp70 genes are located in the C4-H-2D region: possible candidates for the Orch-1 locus [32].
  • However, these results clearly indicate that some minimal amount of Hsp70-1 and/or Hsp70-3 is required for preimplantation embryogenesis, and that increasing the demand for Hsp70s by arsenic exposure heightens this requirement [19].

Analytical, diagnostic and therapeutic context of Hspa1b


  1. Deletion of the inducible 70-kDa heat shock protein genes in mice impairs cardiac contractile function and calcium handling associated with hypertrophy. Kim, Y.K., Suarez, J., Hu, Y., McDonough, P.M., Boer, C., Dix, D.J., Dillmann, W.H. Circulation (2006) [Pubmed]
  2. Effects of hsp70.1 gene knockout on the mitochondrial apoptotic pathway after focal cerebral ischemia. Lee, S.H., Kwon, H.M., Kim, Y.J., Lee, K.M., Kim, M., Yoon, B.W. Stroke (2004) [Pubmed]
  3. Spontaneous activation of pancreas trypsinogen in heat shock protein 70.1 knock-out mice. Hwang, J.H., Ryu, J.K., Yoon, Y.B., Lee, K.H., Park, Y.S., Kim, J.W., Kim, N., Lee, D.H., Jeong, J.B., Seo, J.S., Kim, Y.T. Pancreas (2005) [Pubmed]
  4. Active immunization of mice with an Abeta-Hsp70 vaccine. Koller, M.F., Mohajeri, M.H., Huber, M., Wollmer, M.A., Roth Z'graggen, B.V., Sandmeier, E., Moritz, E., Tracy, J., Nitsch, R.M., Christen, P. Neuro-degenerative diseases. (2004) [Pubmed]
  5. 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration. Waza, M., Adachi, H., Katsuno, M., Minamiyama, M., Sang, C., Tanaka, F., Inukai, A., Doyu, M., Sobue, G. Nat. Med. (2005) [Pubmed]
  6. T-complex polypeptide-1 is a subunit of a heteromeric particle in the eukaryotic cytosol. Lewis, V.A., Hynes, G.M., Zheng, D., Saibil, H., Willison, K. Nature (1992) [Pubmed]
  7. CD40, but not CD40L, is required for the optimal priming of T cells and control of aerosol M. tuberculosis infection. Lazarevic, V., Myers, A.J., Scanga, C.A., Flynn, J.L. Immunity (2003) [Pubmed]
  8. Distinct stimulus-specific histone modifications at hsp70 chromatin targeted by the transcription factor heat shock factor-1. Thomson, S., Hollis, A., Hazzalin, C.A., Mahadevan, L.C. Mol. Cell (2004) [Pubmed]
  9. Hypoglycemia enhances the expression of prion protein and heat-shock protein 70 in a mouse neuroblastoma cell line. Shyu, W.C., Chen, C.P., Saeki, K., Kubosaki, A., Matusmoto, Y., Onodera, T., Ding, D.C., Chiang, M.F., Lee, Y.J., Lin, S.Z., Li, H. J. Neurosci. Res. (2005) [Pubmed]
  10. Induction of antibodies against murine full-length prion protein in wild-type mice. Koller, M.F., Grau, T., Christen, P. J. Neuroimmunol. (2002) [Pubmed]
  11. Overexpression of heat shock protein 70 in R6/2 Huntington's disease mice has only modest effects on disease progression. Hansson, O., Nylandsted, J., Castilho, R.F., Leist, M., Jäättelä, M., Brundin, P. Brain Res. (2003) [Pubmed]
  12. Nonsteroidal anti-inflammatory drugs differentially affect the heat shock response in cultured spinal cord cells. Batulan, Z., Nalbantoglu, J., Durham, H.D. Cell Stress Chaperones (2005) [Pubmed]
  13. Tumor prevention and antitumor immunity with heat shock protein 70 induced by 15-deoxy-delta12,14-prostaglandin J2 in transgenic adenocarcinoma of mouse prostate cells. Vanaja, D.K., Grossmann, M.E., Celis, E., Young, C.Y. Cancer Res. (2000) [Pubmed]
  14. Function and regulation of heat shock factor 2 during mouse embryogenesis. Rallu, M., Loones, M., Lallemand, Y., Morimoto, R., Morange, M., Mezger, V. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  15. Evidence for the involvement of mouse heat shock factor 1 in the atypical expression of the HSP70.1 heat shock gene during mouse zygotic genome activation. Christians, E., Michel, E., Adenot, P., Mezger, V., Rallu, M., Morange, M., Renard, J.P. Mol. Cell. Biol. (1997) [Pubmed]
  16. Heat shock protein-70 mediates the cytoprotective effect of carbon monoxide: involvement of p38 beta MAPK and heat shock factor-1. Kim, H.P., Wang, X., Zhang, J., Suh, G.Y., Benjamin, I.J., Ryter, S.W., Choi, A.M. J. Immunol. (2005) [Pubmed]
  17. Targeted disruption of hsp70.1 sensitizes to osmotic stress. Shim, E.H., Kim, J.I., Bang, E.S., Heo, J.S., Lee, J.S., Kim, E.Y., Lee, J.E., Park, W.Y., Kim, S.H., Kim, H.S., Smithies, O., Jang, J.J., Jin, D.I., Seo, J.S. EMBO Rep. (2002) [Pubmed]
  18. Early transcriptional activation of the hsp70.1 gene by osmotic stress in one-cell embryos of the mouse. Fiorenza, M.T., Bevilacqua, A., Canterini, S., Torcia, S., Pontecorvi, M., Mangia, F. Biol. Reprod. (2004) [Pubmed]
  19. Inhibition of hsp70-1 and hsp70-3 expression disrupts preimplantation embryogenesis and heightens embryo sensitivity to arsenic. Dix, D.J., Garges, J.B., Hong, R.L. Mol. Reprod. Dev. (1998) [Pubmed]
  20. Effects of low-power laser radiation on mice immunity. Novoselova, E.G., Glushkova, O.V., Cherenkov, D.A., Chudnovsky, V.M., Fesenko, E.E. Photodermatology, photoimmunology & photomedicine. (2006) [Pubmed]
  21. CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation. Petrucelli, L., Dickson, D., Kehoe, K., Taylor, J., Snyder, H., Grover, A., De Lucia, M., McGowan, E., Lewis, J., Prihar, G., Kim, J., Dillmann, W.H., Browne, S.E., Hall, A., Voellmy, R., Tsuboi, Y., Dawson, T.M., Wolozin, B., Hardy, J., Hutton, M. Hum. Mol. Genet. (2004) [Pubmed]
  22. Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity. Jana, N.R., Tanaka, M., Wang, G., Nukina, N. Hum. Mol. Genet. (2000) [Pubmed]
  23. Regional distribution of heme oxygenase, HSP70, and glutathione in brain: relevance for endogenous oxidant/antioxidant balance and stress tolerance. Calabrese, V., Scapagnini, G., Ravagna, A., Fariello, R.G., Giuffrida Stella, A.M., Abraham, N.G. J. Neurosci. Res. (2002) [Pubmed]
  24. Brain-derived heat shock protein 70-peptide complexes induce NK cell-dependent tolerance to experimental autoimmune encephalomyelitis. Galazka, G., Stasiolek, M., Walczak, A., Jurewicz, A., Zylicz, A., Brosnan, C.F., Raine, C.S., Selmaj, K.W. J. Immunol. (2006) [Pubmed]
  25. Evidence of an interaction between Mos and Hsp70: a role of the Mos residue serine 3 in mediating Hsp70 association. Liu, H., Vuyyuru, V.B., Pham, C.D., Yang, Y., Singh, B. Oncogene (1999) [Pubmed]
  26. The role of tonicity responsive enhancer sites in the transcriptional regulation of human hsp70-2 in response to hypertonic stress. Heo, J.I., Lee, M.S., Kim, J.H., Lee, J.S., Kim, J., Park, J.B., Lee, J.Y., Han, J.A., Kim, J.I. Exp. Mol. Med. (2006) [Pubmed]
  27. Heat-induced transcription from RNA polymerases II and III and HSF binding activity are co-ordinately regulated by the products of the heat shock genes. Price, B.D., Calderwood, S.K. J. Cell. Physiol. (1992) [Pubmed]
  28. Effects of schisandrin B pretreatment on tumor necrosis factor-alpha induced apoptosis and Hsp70 expression in mouse liver. Ip, S.P., Che, C.T., Kong, Y.C., Ko, K.M. Cell Stress Chaperones (2001) [Pubmed]
  29. Hsp70 inhibits lipopolysaccharide-induced NF-kappaB activation by interacting with TRAF6 and inhibiting its ubiquitination. Chen, H., Wu, Y., Zhang, Y., Jin, L., Luo, L., Xue, B., Lu, C., Zhang, X., Yin, Z. FEBS Lett. (2006) [Pubmed]
  30. Enhanced ubiquitinylation of heat shock protein 90 as a potential mechanism for mitotic cell death in cancer cells induced with hypericin. Blank, M., Mandel, M., Keisari, Y., Meruelo, D., Lavie, G. Cancer Res. (2003) [Pubmed]
  31. HSP70 deficiency results in activation of c-Jun N-terminal Kinase, extracellular signal-regulated kinase, and caspase-3 in hyperosmolarity-induced apoptosis. Lee, J.S., Lee, J.J., Seo, J.S. J. Biol. Chem. (2005) [Pubmed]
  32. Three Hsp70 genes are located in the C4-H-2D region: possible candidates for the Orch-1 locus. Snoek, M., Jansen, M., Olavesen, M.G., Campbell, R.D., Teuscher, C., van Vugt, H. Genomics (1993) [Pubmed]
  33. Protective effect of heat shock proteins 70.1 and 70.3 on retinal photic injury after systemic hyperthermia. Kim, J.H., Kim, J.H., Yu, Y.S., Jeong, S.M., Kim, K.W. Korean journal of ophthalmology : KJO. (2005) [Pubmed]
  34. Genomic instability and enhanced radiosensitivity in Hsp70.1- and Hsp70.3-deficient mice. Hunt, C.R., Dix, D.J., Sharma, G.G., Pandita, R.K., Gupta, A., Funk, M., Pandita, T.K. Mol. Cell. Biol. (2004) [Pubmed]
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