Members of the Hsp70 family form a central hub of the molecular chaperone network, controlling protein homeostasis in prokaryotes and in the ATP-containing compartments of eukaryotic cells. The heat-inducible form Hsp70, its constitutive cytosolic cognate Hsc70, the endoplasmic reticulum form BiP, and the mitochondrial form mHsp70/Mortalin, as well as the more distant Hsp70-related Hsp110s make up 1-2 % of the total mass of soluble proteins in human cells. They can use the energy of ATP-hydrolysis to prevent and forcefully revert the process of polypeptide misfolding and aggregation during and following stress, working as unfoldases to lift aberrant conformers out of kinetic traps. As such, Hsp70s, acting in cooperation with their J-domain co-chaperones and nucleotide exchange factors, constitute a central cellular defense system against cytotoxic misfolded protein conformers that may cause the onset of degenerative diseases, such as Parkinson, Alzheimer, diabetes and aging in general.
In addition to their stress-related functions Hsp70s fulfill many house-keeping functions including de novo folding and maturation of proteins, translocation of precursors across narrow membrane pores into organelles, such as the endoplasmic reticulum, mitochondria or chloroplasts, and control alternative conformations of key regulator proteins involved in signal transduction and cellular control circuits. Hsp70 can also be exposed at the surface of animal cells, where there is presumably no ATP, and apparently serve as specific antigens that are central to cancer immunology.
The purpose of this Research Topic is to gather up-to-date Mini Reviews and Perspective articles that present all the various aspects of Hsp70 action in bacteria and various compartments of eukaryotic cells and on the cellular surface, in optimal growth conditions, as well as, during and following stresses, such as heat-shock and oxidative stress. Contributors should not focus on introducing Hsp70 but rather get straight to the heart of the matter. The aim is to report on how, using the same molecular mechanism, Hsp70 can perform a great diversity of cellular functions, so that we can share and increase our general understanding of this molecular chaperone.
Contributions to this Research Topic can cover:
- Hsp70 as an import/pulling motor in mitochondria, in chloroplasts, and in the endoplasmic reticulum (ER);
- The evolution of DnaK, HscA, Hsp70 and Hsp110 molecules;
- The role of Hsp70 in de novo folding of proteins;
- The role of Hsp70 in the ubiquitination of proteins to be degraded;
- Hsp70 as a de-oligomerizing machine (clathrin);
- Hsp70 as a signal transduction controlling device;
- The role of Hsp70 outside the cell;
- Hsp70 and cancer: anti-Hsp70 therapies;
- Specific inhibitors of Hsp70: how do they differ/complement Hsp90 inhibitors?
- Domain organization and allostery within the Hsp70 molecule;
- The role of J-domain co-chaperones and of NEFs in Hsp70’s specificity;
- The mechanism of Hsp70: effect on bound protein substrate, clamping versus entropic pulling, unfolding versus holding;
- Hsp70’s collaboration with Hsp100/ClpB and with Hsp110/SSE for disaggregation of stable insoluble aggregates;
- Hsp70’s collaboration with Hsp60, Hsp90, Trigger factor and with sHSPs to refold stress-inactivated proteins aggregates.
Members of the Hsp70 family form a central hub of the molecular chaperone network, controlling protein homeostasis in prokaryotes and in the ATP-containing compartments of eukaryotic cells. The heat-inducible form Hsp70, its constitutive cytosolic cognate Hsc70, the endoplasmic reticulum form BiP, and the mitochondrial form mHsp70/Mortalin, as well as the more distant Hsp70-related Hsp110s make up 1-2 % of the total mass of soluble proteins in human cells. They can use the energy of ATP-hydrolysis to prevent and forcefully revert the process of polypeptide misfolding and aggregation during and following stress, working as unfoldases to lift aberrant conformers out of kinetic traps. As such, Hsp70s, acting in cooperation with their J-domain co-chaperones and nucleotide exchange factors, constitute a central cellular defense system against cytotoxic misfolded protein conformers that may cause the onset of degenerative diseases, such as Parkinson, Alzheimer, diabetes and aging in general.
In addition to their stress-related functions Hsp70s fulfill many house-keeping functions including de novo folding and maturation of proteins, translocation of precursors across narrow membrane pores into organelles, such as the endoplasmic reticulum, mitochondria or chloroplasts, and control alternative conformations of key regulator proteins involved in signal transduction and cellular control circuits. Hsp70 can also be exposed at the surface of animal cells, where there is presumably no ATP, and apparently serve as specific antigens that are central to cancer immunology.
The purpose of this Research Topic is to gather up-to-date Mini Reviews and Perspective articles that present all the various aspects of Hsp70 action in bacteria and various compartments of eukaryotic cells and on the cellular surface, in optimal growth conditions, as well as, during and following stresses, such as heat-shock and oxidative stress. Contributors should not focus on introducing Hsp70 but rather get straight to the heart of the matter. The aim is to report on how, using the same molecular mechanism, Hsp70 can perform a great diversity of cellular functions, so that we can share and increase our general understanding of this molecular chaperone.
Contributions to this Research Topic can cover:
- Hsp70 as an import/pulling motor in mitochondria, in chloroplasts, and in the endoplasmic reticulum (ER);
- The evolution of DnaK, HscA, Hsp70 and Hsp110 molecules;
- The role of Hsp70 in de novo folding of proteins;
- The role of Hsp70 in the ubiquitination of proteins to be degraded;
- Hsp70 as a de-oligomerizing machine (clathrin);
- Hsp70 as a signal transduction controlling device;
- The role of Hsp70 outside the cell;
- Hsp70 and cancer: anti-Hsp70 therapies;
- Specific inhibitors of Hsp70: how do they differ/complement Hsp90 inhibitors?
- Domain organization and allostery within the Hsp70 molecule;
- The role of J-domain co-chaperones and of NEFs in Hsp70’s specificity;
- The mechanism of Hsp70: effect on bound protein substrate, clamping versus entropic pulling, unfolding versus holding;
- Hsp70’s collaboration with Hsp100/ClpB and with Hsp110/SSE for disaggregation of stable insoluble aggregates;
- Hsp70’s collaboration with Hsp60, Hsp90, Trigger factor and with sHSPs to refold stress-inactivated proteins aggregates.
