%0 Journal Article
%T Molecular Cochaperones: Tumor Growth and Cancer Treatment
%A Stuart K. Calderwood
%J Scientifica
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/217513
%X Molecular chaperones play important roles in all cellular organisms by maintaining the proteome in an optimally folded state. They appear to be at a premium in cancer cells whose evolution along the malignant pathways requires the fostering of cohorts of mutant proteins that are employed to overcome tumor suppressive regulation. To function at significant rates in cells, HSPs interact with cochaperones, proteins that assist in catalyzing individual steps in molecular chaperoning as well as in posttranslational modification and intracellular localization. We review current knowledge regarding the roles of chaperones such as heat shock protein 90 (Hsp90) and Hsp70 and their cochaperones in cancer. Cochaperones are potential targets for cancer therapy in themselves and can be used to assess the likely prognosis of individual malignancies. Hsp70 cochaperones Bag1, Bag3, and Hop play significant roles in the etiology of some cancers as do Hsp90 cochaperones Aha1, p23, Cdc37, and FKBP1. Others such as the J domain protein family, HspBP1, TTC4, and FKBPL appear to be associated with more benign tumor phenotypes. The key importance of cochaperones for many pathways of protein folding in cancer suggests high promise for the future development of novel pharmaceutical agents. 1. Introduction Chaperones/HSPs. Molecular chaperones are a diverse group of proteins involved in the maintenance of other Ħ°clientĦħ proteins in folded and active conformations in all cellular organisms [1¨C5]. The term molecular chaperone is however generally reserved for proteins with a dedicated role in protein folding and refolding derived from the HSPA (HSP70), HSPB (small HSP), HSPD (Hsp60), HSPC (Hsp90), and HSPH (large HSP) gene families originally discovered as heat shock protein (HSP) genes [2, 6]. Products of these genes direct the folding of much of the proteome, resulting in the formation of proteins or protein complexes capable of metabolic functions in the cell. A subset of these proteins is also expressed at high levels in cells after proteotoxic stresses such as exposure to heat shock, heavy metals, alcohols and sodium arsenite [7¨C10]. Hence, they came to be known as heat shock proteins [7, 10]. Proteotoxic stresses lead to abundant levels of unfolded, aggregated, and ubiquibinated proteins, and cells respond to such an insult by abundant synthesis of HSPs capable of resolving these perturbations to the proteome [11]. These proteins are known to increase cell survival after stress both through direct chaperoning of malfolded proteins as well as inhibition of programmed cell
%U http://www.hindawi.com/journals/scientifica/2013/217513/