Heat shock protein 10 and signal transduction: a “capsula eburnea” of carcinogenesis?

Abstract

To date, little is known either about the physical interactions of heat shock protein 10 (Hsp10) with other proteins within the cell or its involvement in signal transduction pathways. Hsp10 has been considered mainly as a partner of Hsp60 in the Hsp60/10 protein folding machine. Only recently, Hsp10 was reported to interact with proteins involved in deoxyribonucleic acid checkpoint inactivation, termination of M-phase, messenger ribonucleic acid export, import of nuclear proteins, nucleocytoplasmic transport, and pheromone signaling pathways. At the same time, Hsp10 expression can be up-regulated in cancer cells, because it accumulates as the cell transformation progresses. Recent data suggest that Hsp10 may be not only a component of the folding machine but also an active player of the cell signaling network, influencing cell cycle, nucleocytoplasmic transport, and metabolism, with putative roles in the lack of cell differentiation and in the inhibition of apoptosis. In this review, we revise the involvement of Hsp10 in signal transduction pathways and its possible role in cancer etiology.

Effects of cadmium chloride on some mitochondria-related activity and gene expression of human MDA-MB231 breast tumor cells

“…The over-expression of hsp chaperones can depend on Cd-promoted denaturation and oxidation of proteins, and is probably linked to the increase of oxidative stress. Although hsp60 is mostly localized in the mitochondrial matrix, it has also been found in other subcellular localizations including the ER, cell surface, and unidentified vesicles and cytoplasmic granules [57] and also found to be over-expressed and localized in the cytoplasm of cancer cells [58]. In the current study, we report the presence of hsp60 in the cytoplasm of MDA-MB231 tumor cells and demonstrate that CdCl 2 exposure modifies the cytosolic level of the protein.…”

Overexpression of HSP10 in skeletal muscle of transgenic mice prevents the age-related fall in maximum tetanic force generation and muscle cross-sectional area

“…2, A and B). It was important to determine the cellular location of the overexpressed HSP10, since other studies demonstrated that, in large bowel and uterine cancer cells, HSP10 is overexpressed, but the majority of the protein remains in the cytosol (9,11). Isolation of mitochondria from the muscles of adult wild-type and HSP10-overexpressing mice demonstrated that HSP10 was primarily located in the mitochondria (Fig.…”

“…HSP60 and HSP10 together form the HSP60/10 chaperonin complex, which is responsible for the folding of proteins transported into the mitochondrial matrix, refolding, and prevention of aggregation of denatured proteins (12). More recent studies demonstrate chaperone roles for HSP10 that are independent of HSP60, as well as nonchaperone (e.g., signaling) roles for HSP10 (11). HSP10 is encoded by a nuclear gene; the newly translated protein is transported into the mitochondria (18), and HSP10 is mostly localized in the mitochondrial matrix (11).…”

“…More recent studies demonstrate chaperone roles for HSP10 that are independent of HSP60, as well as nonchaperone (e.g., signaling) roles for HSP10 (11). HSP10 is encoded by a nuclear gene; the newly translated protein is transported into the mitochondria (18), and HSP10 is mostly localized in the mitochondrial matrix (11). In contrast, increased content of HSP10 has been observed in the cytosol of some cancer cells (9,10), although the mechanisms by which HSP10 is retained in the cytoplasm in these circumstances are not fully understood (11).…”

Unfolding the relationship between secreted molecular chaperones and macrophage activation states

“…Hsp10 has a range of biological actions both inside cells and when released from stressed cells (reviewed by Czarnecka et al 2006). The concentration of Hsp10 has been measured in the plasma of controls and in patients with chronic periodontal disease undergoing treatment.…”