The heat shock protein 70 (Hsp70) family are a group of chaperones involved in various cellular processes including protein folding and protein degradation. In addition to maintaining normal cellular homeostasis by processing newly synthesized protein, the Hsp70 family is also important in controlling intracellular signaling pathways by regulating the folding and activity of signaling proteins. The various groups within the Hsp70 family are characterized by their expression levels, activities, and subcellular localization (1). For example, the heat shock cognate 70 (Hsc70) group is defined by its constitutive expression and cytoplasmic localization. The Hsp70 group on the other hand is induced by cellular stress such as temperature changes or exposure to toxic chemicals. BiP, another Hsp70 family member, localizes to the ER and acts as a chaperone for secreted or membrane proteins (1). Hsp70 family members contain two domains: the N-terminal ATPase domain and the C-terminal substrate binding domain (1). Hsp70 binds to hydrophobic regions of substrate polypeptides in an ATP-dependent manner. ATP hydrolysis then induces a conformational change in Hsp70 and triggers substrate folding and release (1). The Hsp70 family plays diverse cellular roles in normal cell biology as well as in pathological states. Investigations of these diverse proteins help to clarify their functions and offer potential insight into therapeutic strategies.
Studies using a monoclonal Hsp70/Hsc70 antibody have been successful at characterizing the role of these proteins in chaperone mediated autophagy. A recent study of HIF1-alpha regulation characterized the mechanism of HIF1-alpha degradation. Using Hsp70/Hsc70 antibodies to identify subcellular fractions by western blotting the authors were able to demonstrate HIF1-alpha is degraded in the lysosome through chaperone-mediated autophagy (2). This study was corroborated by a Journal of Biological Chemistry article in which the authors demonstrated a direct interaction between Hsc70 and HIF1-alpha through immunoprecipitation with the Hsp70/Hsc70 antibody (3). In an examination of autophagic vesicular fusion the Hsp70/Hsc70 antibody was used to characterize lysosomes following induction of chaperone mediated autophagy (4). This and other tools used in this study demonstrated the importance of vesicular lipid content during autophagic vesicle fusion. In certain cell types Hsc70 can be found on the surface of cells. In one cell type studied, cell surface Hsc70 rendered these cells vulnerable to rotavirus infection (5). Using the Hsp70/Hsc70 antibody for flow cytometry, the authors of this study demonstrated rotavirus can bind cell surface Hsc70 and facilitate cell entry (5).
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