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proteostasis

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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 present within and outside the cell. Loss of proteostasis is central to understanding the cause of diseases associated with excessive protein misfolding and degradation leading to loss-of-function phenotypes, as well as aggregation-associated degenerative disorders. Therapeutic restoration of proteostasis may treat or resolve these pathologies.

Research

9,492 papers

via PubMed

~15 min read

Article

19 sections
Contents
  • Mechanisms of proteostasis
  • The roles of the ribosome in proteostasis
  • Molecular chaperones and post-translational maintenance in proteostasis
  • Regulating proteostasis by protein degradation
  • Signaling events in proteostasis
  • Cell-autonomous stress responses
  • Cytosolic heat shock response
  • ER unfolded protein response
  • Mitochondrial unfolded protein response
  • Systemic stress signaling
  • Diseases of proteostasis
  • Proteostasis and diseases of protein folding
  • The role of model systems in the elucidation of protein-misfolding diseases
  • Proteostasis and cancer
  • Proteostasis and obesity
  • Proteostasis and aging
  • Pharmacologic intervention in proteostasis
  • See also
  • References

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 present within and outside the cell. Loss of proteostasis is central to understanding the cause of diseases associated with excessive protein misfolding and degradation leading to loss-of-function phenotypes, as well as aggregation-associated degenerative disorders. Therapeutic restoration of proteostasis may treat or resolve these pathologies.

Cellular proteostasis is key to ensuring successful development, healthy aging, resistance to environmental stresses, and to minimize homeostatic perturbations from pathogens such as viruses. Cellular mechanisms for maintaining proteostasis include regulated protein translation, chaperone assisted protein folding, and protein degradation pathways. Adjusting each of these mechanisms based on the need for specific proteins is essential to maintain all cellular functions relying on a correctly folded proteome.

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