Heat shock proteins in multiple myeloma

Abstract

Heat shock proteins are molecular chaperones with a central role in protein folding and cellular protein homeostasis. They also play major roles in the development of cancer and in recent years have emerged as promising therapeutic targets. In this review, we discuss the known molecular mechanisms of various heat shock protein families and their involvement in cancer and in particular, multiple myeloma. In addition, we address the current progress and challenges in pharmacologically targeting these proteins as anti-cancer therapeutic strategies.

Figure 1. The Hsp90 chaperoning system

ATP binding and hydrolysis drive Hsp90 conformational changes resulting in the binding and release of client proteins. Client proteins are presented to Hsp90 by the Hsp70 chaperone complex.

Figure 2. The Hsp70 family proteins

Hsp70 protein isoforms (Bip, cytoplasmic Hsp70s, lys-Hsc70 and mortalin) reside at various subcellular localisations to perform specific roles in protein folding, translocation, degradation and signal transduction, thereby mediating cell survival and apoptosis.

Figure 3. Heat shock proteins contribute to myeloma survival and chemoresistance via their roles in multiple pathways known to be important in myeloma