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The Role of Heat Shock Protein 90 as a Therapeutic Target for Multiple Myeloma

  • Constantine S. Mitsiades
  • Teru Hideshima
  • Nikhil C. Munshi
  • Paul G. Richardson
  • Kenneth C. Anderson
Part of the Contemporary Hematology book series (CH)

Introduction

Heat shock protein 90 (hsp90) is a molecular chaperone ubiquitously present in eukaryotic cells (as reviewed in Neckers and Ivy,1 Xu and Neckers,2 and Workman et al.3). It interacts intracellularly with a broad range of client proteins and functions to preserve their 3-dimensional (3-D) conformation to a functionally competent state, as well as facilitate their intracellular trafficking.4, The interaction of hsp90 with its client proteins involves formation of a multipro-tein complex whereby binding of ATP to the ATP-binding domain of hsp90 allows it to facilitate the proper folding and conformational stabilization of a target protein. In the absence of this ATP hsp90 interaction, client proteins are more likely to remain unfolded or misfolded and become ubiquitinated, thus leading to their proteasomal degradation. Compared to many other heat shock proteins, hsp90 has the intriguing feature that it interacts with a set of client proteins which include cell surface...

Keywords

Multiple Myeloma Heat Shock Protein Hsp90 Inhibitor Client Protein Proteasome Inhibitor Bortezomib 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Constantine S. Mitsiades
    • 1
  • Teru Hideshima
    • 2
  • Nikhil C. Munshi
    • 1
  • Paul G. Richardson
    • 1
  • Kenneth C. Anderson
    • 2
  1. 1.Dana-Farber Cancer InstituteBostonUSA
  2. 2.Department of Medical OncologyJerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute and Harvard Medical SchoolBostonUSA

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