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HSP47: The New Heat Shock Protein Therapeutic Target

  • George Sharbeen
  • Shelli McAlpine
  • Phoebe PhillipsEmail author
Chapter
Part of the Topics in Medicinal Chemistry book series (TMC, volume 19)

Abstract

Heat shock proteins (HSPs) are part of a highly conserved genetic survival system originally discovered by Ferruccio Ritossa in 1962 (Ritossa, Riv Ist Sieroter Ital 37:79–108, 1962). Members of this family function as molecular chaperones that stabilize protein folding (De Maio, Shock 11:1–12, 1999). HSP47 is a molecular chaperone that is essential for collagen biosynthesis (Ishida et al., Mol Biol Cell 17:2346–2355, 2006; Matsuoka et al., Mol Biol Cell 15:4467–4475, 2004; Nagai et al., J Cell Biol 150:1499–1506, 2000). This chaperone is a potential therapeutic target, as it has been observed to be upregulated in collagen-producing cells in several fibrotic conditions (Taguchi et al., Acta Histochem Cytochem 44:35–41, 2011). The recent resolution of a HSP47 crystal structure has provided new insights into the chaperone’s mechanism of action (Widmer et al., Proc Natl Acad Sci U S A 109:13243–13247, 2012) with implications for future drug design. This review will summarize our current understanding of the biochemistry of HSP47-collagen interactions and the potential of HSP47 as a therapeutic target in fibrotic conditions. It will also discuss the current pharmacological inhibitors and the identification of new HSP47 small-molecule inhibitors.

Keywords

Cancer Collagen Fibrosis Hsp47 Serpin 

Notes

Acknowledgments

This work was supported by a Cancer Institute NSW Early Career Fellowship (G. Sharbeen) and a National Health and Medical Research Council (NHMRC) CDF Fellowship (P.A. Phillips).

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • George Sharbeen
    • 1
  • Shelli McAlpine
    • 2
  • Phoebe Phillips
    • 1
    Email author
  1. 1.Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical SchoolUniversity of New South WalesSydneyAustralia
  2. 2.School of ChemistryUniversity of New South WalesSydneyAustralia

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