Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

DNAJB6

  • Shannon E. Weeks
  • Swapnil Bawage
  • Lalita A. Shevde
  • Rajeev S. Samant
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101779

Synonyms

 DJ4;  DnaJ;  HHDJ1;  HSJ-2;  HSJ2;  LGMD1D;  LGMD1E;  MRJ;  MSJ-1

Historical Background

Heat shock proteins were first identified in the late 1970s by Dr. Alfred Tissieres laboratory who noticed that when Drosophila cells in culture were exposed to 37 °C a new set of proteins were synthesized (Arrigo et al. 1980). These proteins have been identified as heat shock proteins (HSP) and play a role in a wide variety of biological processes. Heat shock proteins act as chaperones helping move various client proteins to different cellular compartments. They also ensure the client proteins are folded correctly, as well as aid in degradation of misfolded or damaged proteins (Mitra et al. 2009). Since then, many heat shock proteins have been identified, including DNAJB6. It was initially identified for its role in the development of the embryo and placenta (Hunter et al. 1999). Recently, however, its role in cancer and many other diseases has been investigated.

Structure and Isoforms of...

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Notes

Acknowledgments

NIH R01CA194048 grant to R.S.S.

References

  1. Andrews JF et al. Cellular stress stimulates nuclear localization signal (NLS) independent nuclear transport of MRJ. Exp Cell Res. 2012;318(10):1086–93.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Arrigo AP et al. Localization of the heat shock-induced proteins in Drosophila melanogaster tissue culture cells. Dev Biol. 1980;78(1):86–103.CrossRefPubMedGoogle Scholar
  3. Bhattacharya SD et al. Osteopontin regulates epithelial mesenchymal transition-associated growth of hepatocellular cancer in a mouse xenograft model. Ann Surg. 2012;255(2):319–25.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Cheetham ME, Caplan AJ. Structure, function and evolution of DnaJ: conservation and adaptation of chaperone function. Cell Stress Chaperones. 1998;3(1):28–36.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Comerford KM et al. Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res. 2002;62(12):3387–94.PubMedGoogle Scholar
  6. Dai YS et al. The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells c3 and mediates transcriptional repression through class II histone deacetylase recruitment. Mol Cell Biol. 2005;25(22):9936–48.PubMedPubMedCentralCrossRefGoogle Scholar
  7. De Bock CE et al. Interaction between urokinase receptor and heat shock protein MRJ enhances cell adhesion. Int J Oncol. 2010;36(5):1155–63.PubMedGoogle Scholar
  8. Durrenberger PF et al. DnaJB6 is present in the core of Lewy bodies and is highly up-regulated in parkinsonian astrocytes. J Neurosci Res. 2009;87(1):238–45.CrossRefPubMedGoogle Scholar
  9. Gillis J et al. The DNAJB6 and DNAJB8 protein chaperones prevent intracellular aggregation of polyglutamine peptides. J Biol Chem. 2013;288(24):17225–37.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Hageman J et al. A DNAJB chaperone subfamily with HDAC-dependent activities suppresses toxic protein aggregation. Mol Cell. 2010;37(3):355–69.CrossRefPubMedGoogle Scholar
  11. Hanai R, Mashima K. Characterization of two isoforms of a human DnaJ homologue, HSJ2. Mol Biol Rep. 2003;30(3):149–53.CrossRefPubMedGoogle Scholar
  12. Hunter PJ et al. Mrj encodes a DnaJ-related co-chaperone that is essential for murine placental development. Development. 1999;126(6):1247–58.PubMedGoogle Scholar
  13. Hussein RM et al. Evaluation of the amyloid beta-GFP fusion protein as a model of amyloid beta peptides-mediated aggregation: a study of DNAJB6 chaperone. Front Mol Neurosci. 2015;8:40.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Krishnamachary B et al. Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res. 2003;63(5):1138–43.PubMedGoogle Scholar
  15. Masson C et al. Interaction of the molecular chaperone DNAJB6 with growing amyloid-beta 42 (Aβ42) aggregates leads to sub-stoichiometric inhibition of amyloid formation. J Biol Chem. 2014;289(5):31066–76.CrossRefGoogle Scholar
  16. Menezes ME et al. DNAJB6 governs a novel regulatory loop determining Wnt/beta-catenin signalling activity. Biochem J. 2012;444(3):573–80.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Mitra A et al. Large isoform of MRJ (DNAJB6) reduces malignant activity of breast cancer. Breast Cancer Res. 2008;10(2):R22.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Mitra A et al. Multi-faceted role of HSP40 in cancer. Clin Exp Metastasis. 2009;26(6):559–67.CrossRefPubMedGoogle Scholar
  19. Mitra A et al. DNAJB6 induces degradation of beta-catenin and causes partial reversal of mesenchymal phenotype. J Biol Chem. 2010;285(32):24686–94.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Mitra A et al. DNAJB6 chaperones PP2A mediated dephosphorylation of GSK3beta to downregulate beta-catenin transcription target, osteopontin. Oncogene. 2012a;31(41):4472–83.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Mitra A et al. Micro-RNA-632 downregulates DNAJB6 in breast cancer. Lab Investig. 2012b;92(9):1310–7.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Molkentin JD. Calcineurin-NFAT signaling regulates the cardiac hypertrophic response in coordination with the MAPKs. Cardiovasc Res. 2004;63(3):467–75.CrossRefPubMedGoogle Scholar
  23. Ohtsuka K, Hata M. Mammalian HSP40/DNAJ homologs: cloning of novel cDNAs and a proposal for their classification and nomenclature. Cell Stress Chaperones. 2000;5(2):98–112.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Rose JM et al. Molecular chaperone-mediated rescue of mitophagy by a Parkin RING1 domain mutant. Hum Mol Genet. 2011;20(1):16–27.CrossRefPubMedGoogle Scholar
  25. Ruggieri A et al. Complete loss of the DNAJB6 G/F domain and novel missense mutations cause distal-onset DNAJB6 myopathy. Acta Neuropathol Commun. 2015;3:44.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Sarparanta J et al. Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. Nat Genet. 2012;44(4):450–5 .S451–452PubMedPubMedCentralCrossRefGoogle Scholar
  27. The Huntington’s Disease Collaborative Research Group et al. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. The Huntington’s Disease Collaborative Research Group. Cell. 1993;72(6):971–83.CrossRefGoogle Scholar
  28. Varadarajan S et al. Review: Alzheimer’s amyloid β peptide associated free radical oxidative stress and neurotoxicity. J Struct Biol. 2000;130:184–208.CrossRefPubMedGoogle Scholar
  29. Zhang TT et al. Overexpression of DNAJB6 promotes colorectal cancer cell invasion through an IQGAP1/ERK-dependent signaling pathway. Mol Carc. 2015;54:1205–13.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Shannon E. Weeks
    • 1
  • Swapnil Bawage
    • 1
  • Lalita A. Shevde
    • 1
  • Rajeev S. Samant
    • 1
  1. 1.Division of Molecular and Cellular Pathology, Department of PathologyUniversity of Alabama at BirminghamBirminghamUSA