Chaperome refers to the ensemble of all cellular molecular chaperone and

co-chaperone Co-chaperones are proteins that assist chaperone (protein), chaperones in protein folding and other functions. Co-chaperones are the non-client binding molecules that assist in protein folding mediated by Hsp70 and Hsp90. They are particularly esse ...

proteins that assist

protein folding Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproduci ...

misfolded proteins Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproduci ...

or folding intermediates in order to ensure native protein folding and function, to antagonize aggregation-related

proteotoxicity In medicine, proteinopathy (; 'pref''. protein -pathy 'suff''. disease proteinopathies ''pl''.; proteinopathic ''adj''), or proteopathy, protein conformational disorder, or protein misfolding disease refers to a class of diseases in which certa ...

and ensuing protein loss-of-function or protein misfolding-diseases such as the neurodegenerative diseases Alzheimer's, Huntington's or Parkinson's disease, as well as to safeguard cellular

proteostasis Proteostasis is the dynamic regulation of a balanced, functional proteome. The proteostasis network includes competing and integrated biological pathways within cells that control the biogenesis, folding, trafficking, and degradation of proteins p ...

and proteome balance. The term chaperome was first coined in a 2006 publication in Cell by Balch and co-workers on the finding that down-regulation of the Hsp90 co-chaperone Aha1 rescues misfolding of CFTR in cystic fibrosis to describe the overall chaperone folding environment, or the "chaperome". In 2014, Brehme and co-workers systematically studied the expression dynamics of the full human chaperome comprising ~300 human chaperones and co-chaperones in human aging brains and in brains of patients with neurodegenerative diseases. Integration with chaperome-wide functional RNA interference (RNAi) perturbation experiments in worm and in human cells led to the identification of a chaperome sub-network that safeguards

in aging and neurodegenerative diseases. Recently, a comprehensive literature survey reviewed the literature since the release of the human genome sequence in 2000 for systematic studies in small animal model systems and highlighted the power of model systems to unveil those key chaperone modifiers of proteotoxicity out of the large number represented in the wider human chaperome that could inform targets and strategies for therapeutic regulation of chaperone functionality. In 2016, a ''Nature'' article authored by Rodina et al. introduced a novel term, epichaperome, to refer to a network of existent chaperomes that are found only in cancer cells. More specifically, a few of the major players of this network include heat-shock protein 90 (Hsp90) and heat-shock cognate protein 70 (Hsc70). As opposed to in normal, healthy cells, where these chaperomes are abundant and functional on their own, in cancer cells, changes in the interactions between chaperomes lead to the formation of a network of chaperomes, co-chaperomes, and related co-factors. What has been found is that this strengthened network amongst chaperomes is a mechanism for survival for cancer cells when adapting to stress including hypoxia and heat. The small molecule Hsp90 inhibitor, PU-H71, has been found to have a preferential binding to Hsp90 when it is in the highly integrated complexed form that is the epichaperome.

References

{{Wiktionary Biology terminology * Protein folding

See also

References