Hsp70B' and Hsp72 form a complex in stressed human colon cells and each contributes to cytoprotection.
Hsp70B' is the only major human isoform in the hsp70 family that is strictly stress-inducible, and therefore available to function only in stressed cells. Since Hsp70B' is evolutionarily closely related to human Hsp72, they are thought to function similarly, but direct evidence of Hsp70B' function in stressed cells has been lacking. Here we showed that both Hsp70B' and Hsp72 are essential relatively early after heat stress in the acquisition of cytoprotection by two human colon cell lines. Using flow cytometry to count viable cells, we also showed that cytoprotection is more pronounced in cultures grown at low cell number (LCN), where there is an ample amount of both Hsp70s. siRNA knock-down of either Hsp70B' or Hsp72 severely handicapped the ability of cells to acquire cytoprotection. Hsp70B' and Hsp72 were found to form a complex following stress that included the co-chaperone HOP. These results taken together support the hypothesis that Hsp70B' and Hsp72 play cooperative roles in cell survival of proteotoxic stress. In addition there are implications for chemotherapy protocols and for pathological conditions in which the contributions to cytoprotection of both Hsp70B' and Hsp72 are modulated by cell numbers or density.
Noonan
Emily
E
Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA. emily.noonan@gmail.com
Giardina
Charles
C
Hightower
Lawrence
L
D002452:Cell Count; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003106:Colon / Q000378:metabolism*; D019610:Cytoprotection; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism* / Q000502:physiology*; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism* / Q000502:physiology*; D019073:HT29 Cells; D006360:Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000378:metabolism / Q000502:physiology; D013312:Stress, Physiological / Q000378:metabolism*
D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; C491129:HSPA7 protein, human; D006360:Heat-Shock Proteins; D046912:Multiprotein Complexes; D020033:Protein Isoforms; C079373:STIP1 protein, human